Showing papers on "Sister chromatid exchange published in 1989"
TL;DR: Twenty chemicals were tested for their ability to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (ABs) in cultured Chinese hamster ovary cells (CHO).
Abstract: Forty-six coded chemicals were tested for their ability to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (ABs) in cultured Chinese hamster ovary (CHO) cells using a standard protocol with and without exogenous metabolic activation. Sixteen chemicals were negative and 15 were positive in both assays; 15 were positive for SCEs only (one chemical that was positive for SCEs was equivocal for ABs), and no chemicals induced ABs only. The effect of cell harvest time on the ability to detect the induction of ABs was examined for 18 chemicals. Seven chemicals produced a positive response using both standard and extended harvest times, five were positive only using an extended harvest time, and six were negative using both harvest times. The relationship between cell cycle delay and SCE induction was also examined, and the two appear to be unrelated.
275 citations
TL;DR: Cultivation of human peripheral lymphocytes in the presence of 50-Hz electromagnetic fields does not alter the spontaneous frequencies of sister-chromatid exchanges (SCE) and of chromosomal aberrations (CA), but leads to an enhancement of the cell cycle progression of HPLs in vitro.
Abstract: Cultivation of human peripheral lymphocytes (HPL) in the presence of 50Hz electromagnetic fields (EMFs) does not alter the spontaneous frequencies of sister-chromatid exchanges (SCE) and of chromosomal aberrations (CA), but leads to an enhancement of the cell cycle progression of HPLs in vitro. Pretreatment of HPLs with trenimon (TRN), diepoxybutane (DEB), or methylnitrosournea (MNU) in the G 0 phase of the cell cycle results in dose-dependent elevations of the SCE frequencies. In some cases culturing of HPLs pretreated with MNU or TRN in the presence of EMFs led to significantly higher frequencies of SCEs when compared to cells cultivated in the absence of EMDs. Since we did not use multiple fixation times these data may rather result from differential influences on HPL subsets than from EMF exposure.
143 citations
TL;DR: A system that uses pulsed-field gels for the physical detection of recombinant DNA molecules, double-strand DNA breaks (DSB) and sister-chromatid exchange in the yeast Saccharomyces cerevisiae is described and data on the timing of commitment to meiotic recombination scored genetically is presented.
Abstract: We describe a system that uses pulsed-field gels for the physical detection of recombinant DNA molecules, double-strand DNA breaks (DSB) and sister-chromatid exchange in the yeast Saccharomyces cerevisiae. The system makes use of a circular variant of chromosome III (Chr. III). Meiotic recombination between this ring chromosome and a linear homolog produces new molecules of sizes distinguishable on gels from either parental molecule. We demonstrate that these recombinant molecules are not present either in strains with two linear Chr. III molecules or in rad50 mutants, which are defective in meiotic recombination. In conjunction with the molecular endpoints, we present data on the timing of commitment to meiotic recombination scored genetically. We have used x-rays to linearize circular Chr. III, both to develop a sensitive method for measuring frequency of DSB and as a means of detecting double-sized circles originating in part from sister-chromatid exchange, which we find to be frequent during meiosis.
108 citations
TL;DR: Investigating the influence of 21 kinds of components of plant essence on sister-chromatid exchanges (SCEs) induced by mitomycin C revealed that an alpha,beta-unsaturated carbonyl group may be necessary for SCE-enhancing effects.
106 citations
TL;DR: Benzene and 13 potential metabolites were investigated for genotoxicity in Salmonella typhimurium and V79 Chinese hamster cells and only the trans-1,2-dihydrodiol proved mutagenic in this strain, while the anti-diol epoxide was more potent than the syn-diastereomer.
Abstract: Benzene and 13 potential metabolites were investigated for genotoxicity in Salmonella typhimurium and V79 Chinese hamster cells. In the presence of NADPH-fortified hepatic postmitochondrial fraction (S9 mix), benzene reverted his- S. typhimurium strains. The effect was strongest in strain TA1535. Among the potential metabolites, only the trans-1,2-dihydrodiol, in the presence of S9 mix, and the diol epoxides, in the presence and absence of S9 mix, proved mutagenic in this strain. The anti-diol epoxide was more potent than the syn-diastereomer. Both enantiomers of the anti-diastereomer showed similar activities. S9 mix did not appreciably affect the mutagenicity of the anti-diol epoxide. However, detoxification was observed when purified rat liver dihydrodiol dehydrogenase (EC 1.3.1.20) was used at concentrations comparable to that present in the liver. The (1S)-anti-diol epoxide was a much better substrate than the (1R)-enantiomer, as was true also for (1S)-versus (1R)-trans-1,2-dihydrodiol. The anti-diol epoxide reverted all six strains of S. typhimurium used and induced all four genotoxic effects studied in V79 cells (sister chromatid exchange greater than acquisition of 6-thioguanine resistance, acquisition of ouabain resistance, micronuclei). However, other potential benzene metabolites showed genotoxic effects in V79 cells, as well: sister chromatid exchange was induced by the syn-diol epoxide, 1,2,4-trihydroxybenzene, hydroquinone, catechol, and 1,2,3-trihydroxybenzene. Elevated frequencies of micronucleated cells were observed after treatment with hydroquinone, 1,2,4-trihydroxybenzene, catechol, phenol, 1,2,3-trihydroxybenzene, and quinone. Mutations to 6-thioguanine resistance were induced by quinone, hydroquinone, 1,2,4-trihydroxybenzene, catechol, and the trans-1,2-dihydrodiol.(ABSTRACT TRUNCATED AT 250 WORDS)
93 citations
TL;DR: 2-Hydroxamino-PhIP caused a much larger increase in DNA damage in V79 cells (with hepatocyte activation), whereas MeIQ was more potent with respect to DNA damage induced in hepatocytes and bacteria.
Abstract: Hepatocytes isolated from Aroclor 1254 (PCB) pretreated rats metabolized 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to a reactive metabolite that induced DNA damage measured by alkaline elution or as increased unscheduled DNA synthesis. PhIP induced mutations in Salmonella typhimurium TA98 and DNA strand breaks and sister chromatid exchange(s) in Chinese hamster V79 cells co-incubated with PCB-hepatocytes. No, or only minor genotoxic, effects were observed when hepatocytes from non-induced rats were used. The bacterial mutagenicity could be inhibited by alpha-naphthoflavone, indicating a role of P-450 in the activation of PhIP. At least eight different metabolites could be separated on HPLC after PhIP had been incubated with PCB-hepatocytes. All of the directly acting mutagenicity towards S.typhimurium TA98 co-eluted with one of the metabolites. The identity of this metabolite was concluded to be 2-hydroxamino-PhIP based on the following evidence: (i) it reduced ferric ion to ferrous ion as hydroxylamines do, (ii) it had an identical UV spectrum and chromatographic properties as a species formed upon reduction of 2-nitro-PhIP by NADPH P-450 reductase. This product displayed a major peak at m/z 241 during thermospray mass spectrometry in the positive-ion mode as would be expected from 2-hydroxamino-PhIP. 2-Hydroxamino-PhIP was directly genotoxic both to TA98 and V79 cells. The genotoxic activity of the medium after removing the hepatocytes remained stable for several hours. Compared to 2-amino-3,4-dimethylimidazo[4,5-f]quinolone (MeIQ), PhIP caused a much larger increase in DNA damage in V79 cells (with hepatocyte activation), whereas MeIQ was more potent with respect to DNA damage induced in hepatocytes and bacteria.
91 citations
TL;DR: The induction of chromosomal aberrations and sister-chromatid exchanges (SCE) was studied in human lymphocyte cultures treated with camptothecin (CM), an inhibitor of mammalian topoisomerase I.
Abstract: The induction of chrosomal aberrations and sister-chromatid exchanges (SCE) was studied in human lymphocyte cultures treated with camptothecin (CM), an inhibitor of mammalian topoisomerase I. While no chromosome-type aberrations were found in G 1 -treated cells, instead there was a dose-dependent induction of chromatid-type aberrations. These types of chromosomal alteration were not induced during the treatment itself during the S phase, as CM is not efficiently removed with the normal washing procedure after treatment.
79 citations
Journal Article•
TL;DR: Fire fighters and matched controls were tested for DNA damage which might be related to occupational carcinogen exposures and sensitivity of individual fire fighters to mitomycin C-induced SCE was correlated with number of fires fought in the previous 24 h.
Abstract: Fire fighters are exposed to potentially carcinogenic combustion and pyrolysis products during the course of their work. The present study was designed to test 43 fire fighters and matched controls for DNA damage which might be related to occupational carcinogen exposures. Using peripheral blood lymphocytes, we examined ( a ) baseline sister chromatid exchange (SCE) frequency and ( b ) SCE induction by in vitro mutagenic challenge with mitomycin C. Using nucleated peripheral blood cells, we examined ( c ) polycyclic aromatic hydrocarbon-DNA adduct levels by assessing benzo( a )pyrene diol epoxide (BPDE)-DNA antigenicity. Exposures were determined from histories of fire-fighting activity. The presence of confounding factors ( e.g. , tobacco smoking, charcoalbroiled food consumption, etc.) was determined by questionnaire. Plasma cotinine levels were measured to assess recent exposures to tobacco smoke. White fire fighters exhibited a significantly higher risk for the presence of detectable BPDE-DNA antigenicity than white controls (odds ratio, 3.4; 95% confidence interval, 1.08–10.5 after adjustment). Consumption of charcoal-broiled food 3 times a month did not affect the proportion of positive individuals. Daily alcohol consumption was associated with a larger proportion of individuals exhibiting positive BPDE-DNA antigenicity, ( P = 0.07). Tobacco smoking and charcoal-broiled food consumption, but not fire fighting, were associated with increased levels of baseline SCE. Sensitivity to SCE induced by mitomycin C in cultured peripheral lymphocytes was similar in fire fighter and control groups. However, sensitivity of individual fire fighters to mitomycin C-induced SCE was correlated with number of fires fought in the previous 24 h.
67 citations
TL;DR: Mancozeb exposure was associated with a significant increase in the frequencies of cells with structural chromosome aberrations and sister-chromatid exchanges, and the number of SCEs per cell in short-term cultures of peripheral lymphocytes.
Abstract: Chromosome aberrations and sister-chromatid exchanges (SCEs) were analyzed in short-term cultures of peripheral lymphocytes of 44 workers occupationally exposed to mancozeb during the production of the pesticide Novozir Mn80 and 30 control persons. The results suggest that mancozeb exposure was associated with a significant increase in the frequencies of cells with structural chromosome aberrations (2.07% vs. 1.10% in the controls), and the number of SCEs per cell (9.19 ± 1.81 vs . 7.82 ± 1.04 in the controls).
64 citations
TL;DR: A significant increase in SCEs was observed as the duration of exposure increased and the frequency of M1 metaphases increased significantly whereas M2 and M3+ metaphases decreased in the exposed group.
Abstract: Whole blood of 50 smokers who were exposed to pesticides was set up in RPMI 1640 medium, and observed for sister-chromatid exchanges (SCEs), cell kinetics (CK) and mitotic index (MI). As controls, blood samples were collected from 20 non-smokers (control I) and 27 smokers (control II) who were not exposed to pesticides. A significant increase in SCEs was observed as the duration of exposure increased. The frequency of M 1 metaphases increased significantly whereas M 2 and M 3+ metaphases decreased in the exposed group. The mitotic index increased in control II and in the exposed population while it showed a decrease at 11–25 years' exposure.
63 citations
TL;DR: Two pyrethroid insecticides, cypermethrin and fenvalerate, were tested for their ability to induce chromosome structural aberrations and sister chromatid exchanges in cultured human peripheral blood lymphocytes.
Abstract: Two pyrethroid insecticides, cypermethrin and fenvalerate, were tested for their ability to induce chromosome structural aberrations and sister chromatid exchanges in cultured human peripheral blood lymphocytes. Fenvalerate, but not cypermethrin, increased the frequencies of chromosome-type aberrations and sister chromatid exchanges. In addition, both pyrethroids affected the cell cycle causing a decrease in the proliferative rate index at concentrations greater than 10 micrograms/ml.
Journal Article•
TL;DR: It is suggested that a major biochemical defect resulting from Bloom's syndrome is chronic over-production of the superoxide radical anion, which can apparently inactivate the enzymes responsible for its elimination.
Abstract: We have found that Bloom9s syndrome (BS) cells exhibit elevated levels of superoxide dismutase activity. Since SOD activity has been shown to reflect the intracellular superoxide (O2-) content, these results indicate that BS cells exhibit oxidative stress which ultimately results in DNA damage. Elevated sister chromatid exchange, the major cytological characteristic of BS, and superoxide dismutase induction were simulated in normal lymphoblastoid cells by treatment with compounds that increase the steady-state concentration of O2⨪. The sister chromatid exchange response of a BS lymphoid cell line was modulated through the control of the endogenous O2⨪ content. We therefore suggest that a major biochemical defect resulting from this genetic disorder is chronic over-production of the superoxide radical anion. The consequence of high O2⨪ levels concomitant with induced superoxide dismutase activity is the formation of enormous amounts of H2O2 which can apparently inactivate the enzymes responsible for its elimination. The inefficient removal of peroxide can result in high rates of sister chromatid exchange and chromosomal damage in BS cells and in normal cells treated with oxidation-reduction cycling compounds through the formation of highly reactive intermediary forms of active oxygen.
TL;DR: It is suggested that the inhibition of DNA repair by Ni(II) applies to all DNA changes that are repaired by the 'long-patch' excision repair system and may occur via replacement of other divalent metal ions essential in repair and regulation processes.
Abstract: With regard to contradictory results concerning the mutagenicity of nickel compounds in short-term assays, especially in bacterial test systems, Chinese hamster V79 cells were used to measure mutagenicity, comutagenicity and the induction of sister-chromatid exchanges (SCEs) by NiCl2. We confirmed the induction of mutations at the HGPRT locus as well as SCEs. In addition, NiCl2 shows a pronounced comutagenic effect towards UV. When using confluent cultures or resting cells due to serum deprivation, where more time is given for repair processes, the comutagenic effect is higher compared to logarithmically growing cells (10 and 4 times, respectively, compared to twice). Hence, we attribute this enhancement in mutagenicity to inhibition of DNA repair. Also the increase in induced SCEs after combined treatment with UV and NiCl2 supports this thesis. Furthermore, NiCl2 enhances the cyto-toxicity of cis-DDP about 12-fold. Since no comutagenic effect is observed in combination with MMS, we suggest that the inhibition of DNA repair by Ni(II) applies to all DNA changes that are repaired by the ‘long-patch’ excision repair system. This inhibition may occur via replacement of other divalent metal ions essential in repair and regulation processes.
TL;DR: No adaptation-like response to the induction of chromatid breaks could be demonstrated for lymphocytes of 2 donors pretreated with tritiated thymidine or 0.01 Gy ofX-rays and subsequently exposed to a challenge dose of 1.5 Gy of X-rays.
TL;DR: Results indicate that some risk for mutagenesis may accompany the use of excimer radiation in the UVA region in therapeutic applications.
Abstract: — We compared mutagenesis and sister chromatid exchange (SCE) induction by 193 nm and 308 nm pulsed excimer laser radiation with 254 nm low intensity continuous wave UV light in Chinese hamster ovary (CHO) cells in culture. The 254 nm radiation was most mutagenic of the radiations, in accordance with expectation, and also was most effective in increasing the level of SCEs. The 193 nm radiation was mutagenic at the ouabain resistance locus, but not at the HGPRT locus. However, 193 nm radiation was also strongly cytotoxic at energies producing measurable mutations. This radiation also caused a dose-related increase in SCEs. Pulsed excimer radiation at 308 nm was mutagenic at both loci, and also increased the incidence of SCEs. Comparison of the ratio of mutants/surviving cells at the D37 after radiation showed similar values for 254 nm and 308 nm at the HGPRT locus, but at the ouabain resistance locus, the ratio for the 308 nm radiation was about 5 times that for 254 nm radiation. These results indicate that some risk for mutagenesis may accompany the use of excimer radiation in the UVA region in therapeutic applications.
TL;DR: Various cytogenetic endpoints in both somatic and germ‐line cells from acrylamide‐treated mice were evaluated and sister chromatid exchanges and micronuclei, but not chromosome aberrations, were induced in spleen cells.
Abstract: The industrial chemical acrylamide is suspected to induce potentially heritable genetic damage. While several studies in rodents have indicated that this substance can damage spermiogenic cells, resulting in dominant lethals and heritable translocations, cytogenetic assessments of premeiotic and meiotic cells after exposure have produced equivocal results. In the present study, various cytogenetic endpoints in both somatic and germ-line cells from acrylamide-treated mice were evaluated. Sister chromatid exchanges and micronuclei, but not chromosome aberrations, were induced in spleen cells; synaptonemal complex irregularities (asynapsis), but not chromosome aberrations, were induced in germ cells.
TL;DR: An analog of nalidixic acid with potent topoisomerase II inhibitory activity was selected for examination and proved to be a positive direct‐acting mutagen in the L5178Y/TK+/‐, CHO/ HGPRT, and V79/HGPRT systems.
Abstract: In recent years, evidence has accumulated that suggests that mammalian topoisomerase may play a role in the formation of spontaneous or chemically induced sister chromatid exchange (SCE). In microbial systems, nalidixic acid is known to disrupt the function of a topoisomerase-like enzyme, DNA gyrase. To explore the possible relationship to topoisomerase function and SCE formation in mammalian cells, an analog of nalidixic acid with potent topoisomerase II inhibitory activity was selected for examination in a variety of genetic toxicology assays. This analog, CP-67,015, proved to be a positive direct-acting mutagen in the L5178Y/TK+/-, CHO/HGPRT, and V79/HGPRT systems. However, no gene mutational activity was observed using the Ames test in direct plate, mouse and rat metabolic activation, and mouse urine tests. In vitro cytogenetic studies showed strong clastogenic activity in human lymphocytes and in CHO cells. Compound-induced chromosome damage was also observed in vivo in mouse bone marrow cells. Surprisingly, SCE studies in vitro in human lymphocytes or CHO cells showed only slight increases, even at levels producing severe chromosome breakage. Mouse bone marrow showed no significant elevation of SCE following parenteral treatment with CP-67,015. These results, taken together, demonstrate that CP-67,015 is a direct-acting mutagen in mammalian cells with both gene and chromosomal level effects. The relative ineffectiveness in producing SCEs suggests that CP-67,015 may interfere with a DNA replicative/repair process, perhaps by alteration of one or more DNA polymerase activities. This suggestion is based in part on the known effect of the analog nalidixic acid on DNA gyrase in microbial cells and on topoisomerase in mammalian cells. The profile of genetic activity of CP-67,015, coupled with its inhibitory effect on topoisomerase function, gives rise to a model for SCE formation that is based on anomalies of topoisomerase activity during DNA synthesis.
TL;DR: Observations show that the chromatid-type aberrations and SCEs obtained by exposing unstimulated lymphocytes to m-AMSA were not produced during the treatment itself, but after stimulation at an advanced stage of the cell cycle by an active substance released into the medium during the first hours of incubation.
Abstract: The frequencies of chromosomal aberrations and sister chromatid exchanges (SCE) were studied in human peripheral lymphocytes after exposure of whole blood cultures to the antitumour agent m-AMSA. Chromosome-type aberrations were found in cells exposed before stimulation or during the G1-phase of the cell cycle. Chromatid-type aberrations were obtained in cells exposed during the S- and G2-phases, but also in cells exposed the G1-phase or before stimulation. Treatment of lymphocytes with m-AMSA in the G1-phase or before stimulation had the additional effect of strongly increasing the frequency of SCE. When unstimulated lymphocytes were exposed to m-AMSA, the frequencies of SCE and chromatid-type aberrations, but not the frequency of chromosome-type aberrations, could be strongly reduced by holding the cells in F-10 for 2-4 h before stimulation, or by changing the growth medium after stimulation. A 1-h incubation in growth medium was sufficient for obtaining this reduction. The medium in which the m-AMSA-treated cells were incubated for the first 3 h after stimulation proved to be capable of inducing chromatid-type aberrations in late S/G2-phase and SCEs in the S-phase. These observations show that the chromatid-type aberrations and SCEs obtained by exposing unstimulated lymphocytes to m-AMSA were not produced during the treatment itself, but after stimulation at an advanced stage of the cell cycle by an active substance (m-AMSA or a metabolite of m-AMSA) released into the medium during the first hours of incubation. Post-treatments in G2 with 1-beta-D-arabinofuranosylcytosine (ara-C) and hydroxyurea strongly enhanced the frequency of chromatid-type aberrations obtained after treatment of stimulated or unstimulated lymphocytes with m-AMSA. Post-treatments in unstimulated or G1-phase lymphocytes with ara-C did not influence the frequency of chromosome-type aberrations induced by m-AMSA at these stages, but strongly enhanced those induced by X-rays.
Journal Article•
TL;DR: It is concluded that it is difficult to predict changes in one marker based on changes in another, however, in vitro formation, of PB-derived DNA adducts is consistent over time for individuals.
Abstract: In the present study, benzo( a )pyrene (BP) metabolism, DNA adduct formation, ethoxyresorufin- O -deethylase activity, and sister chromatid exchange induction by BP were compared in human lymphocytes prepared from whole blood of smokers and nonsmokers following an in vitro incubation with BP. There was an approximate 7- to 10-fold variation in all parameters measured. To determine the source of this variation, participants were resampled, the assays were repeated, and all the data were analyzed to assess ( a ) smoking-related effects, ( b ) differences in multiple samples from the same individual, and ( c ) intraindividual, experimental, and interindividual variation. No smoking-related effects were observed except for baseline sister chromatid exchange frequency. The variation observed for BP-related DNA adducts and ethoxyresorufin- O -deethylase activity was primarily due to interindividual variation. For example, in vitro formation of DNA adducts did not change when samples were obtained at different times from the same individual and were not influenced significantly by culture conditions. No significant correlation existed between DNA adduct formation and BP metabolism [correlation coefficient ( r ) = 0.27] for either the total population or when segregated based on smoking status. Furthermore, no correlation was seen between DNA adducts and sister chromatid exchange induction by BP. Our studies have compared a number of commonly used lymphocyte markers and conclude that it is difficult to predict changes in one marker based on changes in another. However, in vitro formation of BP-derived DNA adducts is consistent over time for individuals.
TL;DR: This finding indicates that dioxin impurities do not account for the peroxisome proliferation induced by chlorophenolate, and the pattern of induction of xenobiotic metabolizing enzymes showed some differences betweenchlorophenolate treatment and 2,3,7,8-TCDD treatment.
Abstract: The induction of hepatic peroxisome proliferation and drug metabolizing enzymes and of sister chromatid exchange (SCE) in lymphocytes was studied in male Han/Wistar rats after exposing them for 2 weeks to a commercial chlorophenolate formulation (Ky-5) (100mg/kg/ day), to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; 0.05–5 μg/kg/wk) and to the pure phenoxyacetic acids, 2,4-dichlorophenoxyacetic acid (2,4-D; 100 mg/kg/day) and 2-chloro-4-methylphenoxyacetic acid (MCPA; 100 mg/kg/day). The chlorophenolate formulation and pure 2,4-D and MCPA caused significant increases in the number of peroxisomes in liver cells, although the average size of peroxisomes was not affected, whereas the effect of even the highest dose of 2,3,7,8-TCDD remained small. This finding indicates that dioxin impurities do not account for the peroxisome proliferation induced by chlorophenolate. The relative weight of the liver increased significantly in rats treated with the chlorophenolate formulation and with 2,3,7,8-TCDD (5.0 and 0.5 μg/kg). The pattern of induction of xenobiotic metabolizing enzymes showed some differences between chlorophenolate treatment and 2,3,7,8-TCDD treatment. Furthermore, the effects of pure phenoxyacetic acids were different from that seen with chlorophenolate and 2,3,7,8-TCDD. The highest dose of 2,3,7,8-TCDD increased the frequency of SCE in circulating lymphocytes slightly, but significantly.
TL;DR: Present studies clearly proves the genotoxic potential of both NNN and NNK and between the two NNK is more potent.
TL;DR: Combinations of oxygen radical scavengers and antioxidants significantly reduced the number of sister-chromatid exchanges in Chinese hamster ovary cells exposed to human phagocytes stimulated to generate oxygen radicals.
Abstract: Combinations of oxygen radical scavengers and antioxidants significantly reduced the number of sister-chromatid exchanges in Chinese hamster ovary cells exposed to human phagocytes stimulated to generate oxygen radicals. When vitamin E was combined with these antioxidants, no increase in sister-chromatid exchanges was observed compared to controls.
TL;DR: Three pairs of structurally similar carcinogenic/ non‐carcinogenic chemicals were tested for in vivo genotoxic activity in B6C3F1 mice, and o‐toluidine hydrochloride increased the frequency of sister chromatid exchanges in two successive trials, while o‐anthranilic acid had a positive effect on sister Chromatid exchange in two of three trials.
Abstract: Three pairs of structurally similar carcinogenic/ non-carcinogenic chemicals were tested for in vivo genotoxic activity in B6C3F1 mice. The carcinogenic/non-carcinogenic pairs, respectively, were o-toluidine hydrochloride/o-anthranilic acid, 4-chloro-o-phenylenediamine/4-nitro-o-phenylenediamine, and 3-(chloromethyl)pyridine hydrochloride/2-(chloromethyl)pyridine hydrochloride. Bone marrow cells from mice given intraperitoneal injections of up to the maximum tolerated dose were evaluated for chromosomal aberration, sister chromatid exchange, and micronucleus induction, o-anthranilic acid and o-toluidine hydrochloride did not increase the frequency of chromosomal aberrations or micronuclei. o-Toluidine hydrochloride increased the frequency of sister chromatid exchanges in two successive trials, while o-anthranilic acid had a positive effect on sister chromatid exchanges in two of three trials. Both 2-(chloromethyl) and 3-(chloromethyl)pyridine hydrochloride were negative for all three endpoints. Assays for chromosomal aberrations and micronuclei each distinguished between 4-chloro-o-phenylenedi-amine and its non-carcinogenic companion, 4-nitro-o-phenylenediamine. In the aberration test, 4-chloro-o-phenylenediamine produced a few cells with very large numbers of aberrations rather than an even distribution of damage among cells.
TL;DR: It is concluded that mammalian cells with both intact repair and enzyme systems are more relevant than bacterial systems for evaluating the carcinogenic potential of heterocyclic amines.
Abstract: Two of the major bacterial mutagens formed in heated meat products, 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or the basic fraction of beef extract induced a low frequency of sister chromatid exchanges in human lymphocyte cultures in the presence of metabolic activation. Structural chromosome aberrations were not induced at comparable high concentrations in human lymphocytes with intact repair system, suggesting that repair or induction of point mutations are involved in the DNA-damaging effect of heterocyclic amines rather than structural chromosome aberrations. Accordingly it may be concluded that mammalian cells with both intact repair and enzyme systems are more relevant than bacterial systems for evaluating the carcinogenic potential of heterocyclic amines.
TL;DR: The cytotoxicity, mutagenicity and transforming potentials of three second generation platinum compounds have been investigated in mammalian cells and cisplatin was highly carcinogenic, followed by spiroplatin, and carboplatin and iproplatin were potentially weak carcinogens.
TL;DR: Human peripheral blood lymphocytes from 10 male donors were exposed to mitomycin C with and without prior irradiation with 0.01 Gy X-rays and an acute or chronic irradiation of lymphocytes in G1 resulted in a decrease in the subsequent level of mitomycus C-induced sister-chromatid exchange aberrations.
TL;DR: Kinetin itself had no significant effect on SCE induction, but there was a tendency that SCEs induced by 2,4,5-T were suppressed by kinetin.
Abstract: In order to know the mutagenic effects of synthetic auxins (NAA, 2,4-D, and 2,4,5-T) and a cytokinin (kinetin) in vitro, sister chromatid exchanges (SCEs) were analyzed in cultured cells of a hexaploid wheat (Triticum aestivum L.). In the MS medium supplemented with 2.0 mg/l 2,4-D, the mean number of SCEs per cell was 15.2, and per pg of DNA, 0.42. No significant effect was found in the treatments of NAA or 2,4-D at concentrations of 0.5–10.0 mg/l, whereas more than 2.0 mg/l of 2,4,5-T induced dramatic increases of SCEs. Kinetin itself had no significant effect on SCE induction, but there was a tendency that SCEs induced by 2,4,5-T were suppressed by kinetin.
TL;DR: Results on the growth kinetics and cytogenetic characteristics offered the high possibility of the use of this cell line as a suitable in vitro model for clastogenicity studies in fish.
Abstract: A cell line (ULF-23HU) from the fin of the central mudminnow (Umbra limi) was characterized and tested for its suitability to assess cytogenetic damages induced by chemicals in fish. Cells of this line exhibit a fibroblastlike appearance and grew optimal at 25°C in, TC-199 medium containing 10% fetal bovine serum, but slower growth continued down to 4°C, where they could be stored for prolonged periods. Seeding efficiency of ULF-23HU cells on the plastic substratum was approximately 85% in the above culture medium at 25°C. They had a 32-h cell cycle time taken up by a 20-h S period as determined by the autoradiographic analysis of the fraction of labeled mitosis. Cultures showed relatively high mitotic index (0.84 to 2.35%) during exponential growth phase lasting about 7 d. Karyological analysis of the cells at the different subculture passages revealed constant chromosome modal number of 23 consisting of metacentric or submetacentric chromosomes, which were primarily similar to those of in vivo cells, with one additional chromosome. The spontaneous sister chromatid exchange rate was 5.3 per metaphse. When ULF-23HU cells were exposed toN-nitroso-N-methylurea, a clastogen in the mammalian cells, dose-dependent increases both in sister chromatid exchanges and chromosome aberrations were clearly detected. These results on the growth kinetics and cytogenetic characteristics offered the high possibility of the use of this cell line as a suitable in vitro model for clastogenicity studies in fish.
TL;DR: It is of interest that Ames Salmonella results are consistent with in vivo genotoxicity for these compounds and only the plate test version of the Ames procedure is consistent with this order.
Abstract: Sister-chromatid exchange (SCE) and chromosome aberrations (CA) in bone marrow cells were analyzed after in vivo exposure in mice to 4 aliphatic epoxides, namely 1-naphthyl glycidyl ether (NGE), 1-naphthyl propylene oxide (NPO), 4-nitrophenyl glycidyl ether (NPGE) and trichloropropylene oxide (TCPO). These compounds were selected as being among the most mutagenic aliphatic epoxides in our previous structure-mutagenicity studies with the Ames test. There were significant dose-related increases in SCE and CA results for all 4 epoxides. The order of genotoxicity as established through SCE was NGE > NPO > NPGE ≅ TCPO > solvent control. It is of interest that Ames Salmonella results are consistent with in vivo genotoxicity for these compounds. However, only the plate test version of the Ames procedure is consistent with this order of in vivo genotoxicity and neither preincubation Ames testing results nor chemical alkylation rates would have predicted this order.
TL;DR: Results show that the genotoxic effects of paraquat and diquat occur not only at high concentrations, but also at concentrations low enough to stimulate the cell-cycle rate.