Showing papers on "Sister chromatid exchange published in 2002"

Targeted inactivation of p53 in human cells does not result in aneuploidy.

Abstract: Because p53 mutation and aneuploidy usually coexist, it has been suggested that p53 inactivation leads to aneuploidy. We have rigorously tested this hypothesis in diploid human cell lines in which p53 was experimentally inactivated by targeted homologous recombination. Cells completely deficient in p53 did not become aneuploid, although a slight tendency toward tetraploidization was observed. No increased rates of numerical or structural chromosomal instabilities were observed in the p53-deficient cells. Rates of sister chromatid exchange and homologous recombination were also unaffected by p53 status. These results show that inactivation of p53 does not, in and of itself, lead to the development of aneuploidy.

Genotoxic effects of malathion: an organophosphorus insecticide, using three mammalian bioassays in vivo

Abstract: The genotoxic effects of malathion was evaluated using chromosome aberration, sister chromatid exchange (SCE) and sperm abnormality assays in mice. All the three acute doses (2.5, 5 and 10 mg/kg) of malathion tested in the present study, induced significant dose-dependent increase in the frequency of chromosome aberrations and sperm abnormalities, but did not affect the total sperm count. The highest acute dose induced a >12-fold increase in the frequency of chromosome aberrations, two-fold increase in the frequency of SCEs and four-fold increase in the frequency of sperms with abnormal head morphology following intraperitoneal (i.p.) exposure. Further, a significant increase in the frequency of SCEs was observed, but the increase was not dose-dependent. At higher doses, malathion induced a moderate delay in cell cycle as evident from the increase in average generation time (AGT). The present findings suggest that technical grade malathion is a potent genotoxic agent and may be regarded as a potential germ cell mutagen also.

Werner and Bloom helicases are involved in DNA repair in a complementary fashion

Abstract: Werner syndrome (WS) is a recessive disorder characterized by premature senescence. Bloom syndrome (BS) is a recessive disorder characterized by short stature and immunodeficiency. A common characteristic of both syndromes is genomic instability leading to tumorigenesis. WRN and BLM genes causing WS and BS, encode proteins that are closely related to the RecQ helicase. We produced WRN−/−, BLM−/− and WRN−/−/BLM−/− mutants in the chicken B-cell line DT40. WRN−/− cells showed hypersensitivities to genotoxic agents, such as 4-nitroquinoline 1-oxide, camptothecin and methyl methanesulfonate. They also showed a threefold increase in targeted integration rate of exogenous DNAs, but not in sister chromatid exchange (SCE) frequency. BLM−/− cells showed hypersensitivities to the genotoxic agents as well as ultraviolet (UV) light, in addition to a 10-fold increase in targeted integration rate and an 11-fold increase in SCE frequency. In WRN−/−/BLM−/− cells, synergistically increased hypersensitivities to the genotoxic agents were observed whereas both SCE frequencies and targeted integration rates were partially diminished compared to the single mutants. Chromosomal aberrations were also synergistically increased in WRN−/−/BLM−/− cells when irradiated with UV light in late S to G2 phases. These results suggest that both WRN and BLM may be involved in DNA repair in a complementary fashion.

Effects on sister chromatid exchange frequency of polymorphisms in DNA repair gene XRCC1 in smokers

Abstract: The association between metabolic polymorphisms and cigarette smoking-induced cancers has been documented. However, the role of DNA repair polymorphism in carcinogenesis is less clear. To investigate if the polymorphisms of metabolic traits and DNA repair modulate smoking-related DNA damage, we used sister chromatid exchange (SCE) as a marker of genetic damage to explore the relationship of microsomal epoxide hydrolase (mEH), glutathione S-transferase M1 (GSTM1), and X-ray cross-complementing group 1 (XRCC1) and cigarette smoking-induced SCE. Sixty-one workers without significant exposure to mutagens were recruited. Questionnaires were completed to obtain detailed occupational, smoking, and medical histories. SCE frequency in peripheral lymphocytes was determined using a standard cytogenetic assay and GSTM1, mEH (exons 3 and 4), XRCC1 (codon 399) genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP). Smokers had higher SCE frequency than non-smokers (8.4 versus 7.1, P<0.05). Among workers who had smoked equal to or greater than 10 cigarettes each day, those with XRCC1 Arg/Gln+Gln/Gln had higher SCE frequency than those with XRCC1 Arg/Arg after adjusting for potential confounders (9.0 versus 7.9, P<0.05). The interaction of XRCC1 and cigarettes smoked per day on SCE frequency was also observed (P=0.02). There was no significant interaction between cigarettes smoked per day with GSTM1 and mEH on SCE frequency. Our results support previous epidemiological studies that XRCC1 may play a role in cigarette smoking-induced lung cancer.

Involvement of membrane signaling in the bystander effect in irradiated cells.

Abstract: We have shown previously that when confluent cultures of mammalian cells are exposed to very low fluences of alpha particles, fluences whereby only 1-3% of the cell nuclei are traversed by a particle, genetic effects, including specific gene mutations and sister chromatid exchanges, are induced in neighboring, nonirradiated ("bystander") cells (H. Nagasawa and J. B. Little, Cancer Res., 52: 6394-6396, 1992; H. Nagasawa and J. B. Little, Radiat. Res., 152: 552-557, 1999). The present experiments were designed to determine whether signaling pathways arising in the cell membrane may mediate this effect. Cells were irradiated in the presence of Filipin, an agent that disrupts lipid rafts, effectively inhibiting membrane signaling, and the induction of sister chromatid exchange and HPRT mutations by very low fluences of alpha particles (mean doses 0.17-0.5 cGy) was measured. Filipin completely suppressed the induction of both genetic effects in bystander cells. After exposure to 10 cGy, when most mutations occurred in directly irradiated cells, no suppressive effect of Filipin was observed. These results suggest that membrane signaling may play an important role in the bystander effect of radiation. On the other hand, the effects in directly irradiated cells do not appear to be mediated via the cell membrane.

Vanadate induces DNA strand breaks in cultured human fibroblasts at doses relevant to occupational exposure.

Abstract: To study possible genotoxic effects of occupational exposure to vanadium pentoxide, we determined DNA strand breaks (with alkaline comet assay), 8-hydroxy-2'deoxyguanosine (8-OHdG) and the frequency of sister chromatid exchange (SCE) in whole blood leukocytes or lymphocytes of 49 male workers employed in a vanadium factory in comparison to 12 non-exposed controls In addition, vanadate has been tested in vitro to induce DNA strand breaks in whole blood cells, isolated lymphocytes and cultured human fibroblasts of healthy donors at concentrations comparable to the observed levels of vanadium in vivo To investigate the impact of vanadate on the repair of damaged DNA, co-exposure to UV or bleomycin was used in fibroblasts, and DNA migration in the alkaline and neutral comet assay was determined Although, exposed workers showed a significant vanadium uptake (serum: median 538microg/l, range 218-4635microg/l) no increase in cytogenetic effects or oxidative DNA damage in leukocytes could be demonstrated This was consistent with the observation that in vitro exposure of whole blood leukocytes and lymphocytes to vanadate caused no significant changes in DNA strand breaks below concentrations of 1microM (50microg/l) In contrast, vanadate clearly induced DNA fragmentation in cultured fibroblasts at relevant concentrations Combined exposure of fibroblasts to vanadate/UV or vanadate/bleomycin resulted in non-repairable DNA double strand breaks (DSBs) as seen in the neutral comet assay We conclude that exposure of human fibroblasts to vanadate effectively causes DNA strand breaks, and co-exposure of cells to other genotoxic agents may result in persistent DNA damage

Cytogenetic effects of hexavalent chromium in Bulgarian chromium platers.

Abstract: The aim of the present study was to evaluate the genotoxic effects of hexavalent chromium (Cr(VI)) in vivo in exposed Bulgarian chromium platers by using classical cytogenetic and molecular cytogenetic analyses of peripheral lymphocytes and exfoliated buccal cells. No significant difference was observed between the exposed workers and the controls with regard to the frequency of cells with chromosome aberrations (CAs) using conventional Giemsa staining and in the frequency of sister chromatid exchanges (SCEs). However, there was a significant increase in the number of cells with micronuclei (MN) in peripheral lymphocytes from chromium exposed workers as compared to the controls. In the buccal cells from these workers, this increase was even more pronounced. Cytosine arabinoside (AraC), an inhibitor of DNA synthesis and repair, was found to significantly increase the levels of MN in vitro in the lymphocytes of both groups. The increase was more expressed in the lymphocytes of chromium exposed workers. Both centromere positive (C(+)) as well as centromere negative (C(-)) MN were observed by the fluorescence in situ hybridization (FISH) technique in both of the cell types studied. No difference between C(+) and C(-) MN frequencies was found in the lymphocytes as well as in the buccal cells. Thus, Cr(VI) appears to have both clastogenic as well as aneugenic effects in humans.

The 4'-hydroxy group is responsible for the in vitro cytogenetic activity of resveratrol.

Abstract: We previously reported that 3,5,4'-trihydroxy-trans-stilbene (resveratrol), a polyphenolic phytoalexin found in grapes, induces a high frequency of sister chromatid exchanges (SCEs) in vitro. In this study, to investigate structure activity relationships, we synthesized six analogues of resveratrol differing in number and position of hydroxy groups, and we investigated their activity in chromosomal aberration (CA), micronucleus (MN) and sister chromatid exchange (SCE) tests in a Chinese hamster cell line (CHL). Two of the six analogues (3,4'-dihydroxy-trans-stilbene and 4-hydroxy-trans-stilbene) showed clear positive responses in a concentration-dependent manner in all three tests. Both were equal to or stronger than resveratrol in genotoxicity. The 4'-hydroxy (OH) analogue had the simplest chemical structure and was the most genotoxic. The other analogues did not have a 4'-hydroxy group. These results suggested that a 4'-hydroxy group is essential to the genotoxicity of stilbenes.

Sister chromatid exchange in pathology staff occupationally exposed to formaldehyde

Abstract: Sister chromatid exchange (SCE) was measured in peripheral lymphocytes of 90 workers from 14 hospital pathology departments in Israel who were occupationally exposed to formaldehyde (FA) and of 52 unexposed workers from the administrative section of the same hospitals. The mean exposure period to FA was 15.4 years (range 1–39). The results of SCEs are expressed in two variables: (a) mean number of SCEs per chromosome and (b) proportion of high frequency cells (cells with more than eight SCEs). A high correlation was found between these two variables. The adjusted means of both SCEs variables were significantly higher among the exposed compared with that of the unexposed group (P Our finding of a significant increase of SCEs frequency in peripheral lymphocytes in pathology staff indicates a potential cytogenetic hazard due to FA exposure. We conclude that our data indicate that FA is mutagenic to humans.

Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents

Abstract: We examined sister chromatid exchanges (SCEs) and micronuclei (MN; cytokinesis-block method) in cultured peripheral lymphocytes from 52 female workers of two shoe factories and from 36 unexposed age- and sex-matched referents. The factory workers showed an elevated level of urinary hippuric acid, a biomarker of toluene exposure, and workplace air contained high concentrations of various organic solvents such as toluene, gasoline, acetone, and (in one of the plants only) ethylacetate and methylenediphenyl diisocyanate. The shoe factory workers showed a statistically significant higher frequency of micronucleated binucleate lymphocytes in comparison with the referents. This finding agreed with three preliminary MN determinations (each comprising 27-32 shoe workers and 16-20 controls) performed in one of the plants 2-5 years earlier. The shoe factory workers also had a lower average level of blood hemoglobin than the referents. In contrast, no difference was found between the groups in SCE analysis. Smokers showed significantly higher mean frequencies of SCEs per cell and high frequency cells (HFC) than nonsmokers. Aging was associated with increased MN rates and reduced cell proliferation. Polymorphism of the glutathione S-transferase M1 gene (GSTM1) did not affect the individual level of SCEs; but in smoking shoe workers an effect of the occupational exposure on the frequency of micronucleated cells could be seen only in GSTM1 null subjects. The low prevalence of the glutathione S-transferase T1 (GSTT1) null genotype precluded the evaluation of the influence of GSTT1 polymorphism. Our results show that the shoe factory workers have experienced genotoxic exposure, which is manifest as an increase in the frequency of MN, but not of SCEs, in peripheral lymphocytes. The exposures responsible for the MN induction could not be identified with certainty, but exposure to benzene in gasoline and methylenediphenyl diisocyanate may explain some of the findings.

Fenvalerate-induced chromosome aberrations and sister chromatid exchanges in the bone marrow cells of mice in vivo

Abstract: Fenvalerate, a synthetic pyrethroid insecticide, is commonly used in agriculture and other domestic applications due to its high insecticidal activity and low mammalian-, avian- and phyto-toxicities However, the genotoxic effect of fenvalerate is highly equivocal In the present study the genotoxic effects of fenvalerate was evaluated using structural chromosome aberration (CA) and sister chromatid exchange (SCE) assays in mice Out of the three doses (5, 10 and 20 mg/kg) tested, statistically significant increase in CA was found following intra peritoneal (ip) treatment of 20 mg/kg of fenvalerate for 24 h (P 5×4 mg / kg ) of fenvalerate could induce any significant effect All the three acute doses induced significant increase in the frequency of SCEs (P

Low frequency noise and whole-body vibration cause increased levels of sister chromatid exchange in splenocytes of exposed mice

Abstract: Chronic exposure to low frequency (LF) noise and whole-body vibration (WBV) induces both physiological and psychological alterations in man. Recently, we have shown that long-term occupational exposure to LF noise and WBV produces genotoxic effects in man expressed as an increase in sister chromatid exchange (SCE) levels in lymphocytes. The objectives of the present study were to investigate whether the observed effect could be reproduced in a murine model and, if so, which of the agents, LF noise alone or in combination with WBV, would be instrumental in the SCE induction. SCEs were analyzed in spleen lymphocytes of mice exposed to LF noise alone and in combination with WBV for 300 and 600 hr. An effect at the cell cycle kinetics level was also investigated. The results revealed significant increases in the mean SCE number per cell and in the proportion of cells with high frequency of SCEs (HFCs) in lymphocytes of mice submitted to combined noise and WBV over controls. No significant differences were found between single noise-exposed and control mice. A cell cycle delay was observed exclusively in the noise and WBV exposure groups. In conclusion, we demonstrated that, as in exposed workers, prolonged exposure to the combination of LF noise and WBV determines an increase in SCE level in mice while LF noise alone is not effective in SCE induction.

Correlations of Blood Lead with DNA-Protein Cross-Links and Sister Chromatid Exchanges in Lead Workers

Abstract: Levels of sister chromatid exchanges (SCEs), high-SCE frequency cells (HFCs), DNA-protein cross-links (DPCs), blood lead (BLL), and zinc protoporphyrin (ZPP) were measured in peripheral blood from three groups. The lead workers were divided into two groups: a high BLL group (≥15μg/dl) and a low BLL group ( 15 μg/dl, of which, 3 exceeded current exposure limits (≥40 μg/dl). The BLL levels of all 11 controls were <15 μg/dl. The average SCE and DPC values for the workers were 6.1 SCEs/cell and 1.9%, which were significantly higher ( P < 0.01, Wilcoxon’s test) than the value of 5.2 SCEs/cell and 1.1% for the control subjects. Lead workers had significantly higher BLL and ZPP levels than did the controls. Statistically significant increases in DPCs, SCEs, and HFCs were observed for the high-BLL group compared with the control group. The results of this study suggest that DPCs, SCEs, and HFCs are reliable biomarkers for monitoring workers exposed to lead and clearly indicate health effects from occupational exposure to lead.

Influence of GSTM1 and GSTT1 genotypes on sister chromatid exchange induction by styrene in cultured human lymphocytes

Abstract: Glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) are polymorphically expressed in humans; about 47% and 13% of Finns lack the GSTM1 and GSTT1 activity due to homozygous deletion of the respective genes (null genotypes). We previously observed that GSTT1 null genotype was associated with increased induction of sister chromatid exchanges (SCEs) by a metabolite of styrene, styrene-7,8-oxide, in human lymphocyte cultures, while GSTM1 genotype had no effect. In the present study, we examined the potential effect of these genotypes on SCE induction by the parent compound styrene. Seventy-two hour whole-blood lymphocyte cultures from 24 healthy human donors, representing all different combinations of these genotypes, were examined. In agreement with our earlier findings, styrene was an efficient inducer of SCEs in cultures of all donors. In two separate experiments, the mean number of SCEs/cell induced by 1.5 mM styrene was 1.55 times (P = 0.011) or 1.34 times (P = 0.015) higher in subjects lacking both GSTM1 and GSTT1 than in subjects having both genes. Donors null for only one of the genes showed intermediate SCE induction by styrene. At 0.5 mM styrene, no clear differences in SCE rates among the genotypes were seen. Our results suggest that the concurrent lack of the GSTM1 and GSTT1 genes increases the genotoxic effects of styrene in human cells. The discrepant findings obtained for the importance of GSTM1 genotype in modulating the genotoxic effects induced by styrene-7,8-oxide and styrene may reflect a difference between a direct treatment with styrene-7,8-oxide and its formation from styrene in the cells. Although glutathione conjugation is a minor route in styrene detoxification in human liver in vivo, individual sensitivity associated with GSTM1 and GSTT1 null genotypes may be important locally in blood circulation and in blood-forming organs.

Analysis of DNA and hemoglobin adducts and sister chromatid exchanges in a human population occupationally exposed to propylene oxide: a pilot study.

Abstract: Propylene oxide (PO), a simple alkylating agent used in the chemical industry, is weakly genotoxic and induces nasal cavity tumors in rodents on inhalation at high air concentrations. DNA adducts, hemoglobin adducts, and sister chromatid exchanges (SCE) were analyzed as biomarkers of exposure in a group of eight PO-exposed workers and eight nonexposed subjects. 1-2-Hydroxypropyladenine (1-HP-adenine) in DNA of WBCs was analyzed using a hypersensitive 32P-postlabeling assay. HP-valine in hemoglobin was measured using gas chromatography/tandem mass spectrometry. Air measurements indicated PO levels in the range of 1–7 ppm. All three biomarkers showed significantly increased levels in the exposed workers. 1-HP-adenine was recorded in seven of the exposed workers (mean 0.66 mol/109 mol nucleotides) but was not detected in any of the control subjects. HP-valine was found in all subjects (means of 2.7 and 0.006 pmol/mg globin in exposed workers and controls, respectively). The average frequencies of SCE were 3.7/cell in exposed workers and 2.0/cell in controls, respectively. DNA and hemoglobin adducts were correlated ( r = 0.887), as well as DNA adducts and SCE ( r = 0.792) and hemoglobin adducts and SCE ( r = 0.762). The present study is the first demonstrating PO-DNA adducts in human individuals. It is also the first study indicating cytogenetic effects in humans from PO exposure, although confounding effects from other sources cannot be excluded.

Genetic toxicology studies with glutaraldehyde

Abstract: Glutaraldehyde (GA; CAS no. 111-30-8) has a wide spectrum of industrial, scientific and biomedical applications, with a potential for human exposure particularly in its biocidal applications. The likelihood for genotoxic effects was investigated in vitro and in vivo. A Salmonella typhimurium reverse mutation assay showed no evidence for mutagenic activity with strains TA98, TA1535, TA1537 and TA1538, with or without metabolic activation. However, there was a weak mutagenic response (1.9–2.3-fold at the highest non-toxic concentration) with TA100 in the presence of metabolic activation. In a Chinese hamster ovary (CHO) forward gene mutation assay (HGPRT locus) there were no consistent, statistically significant, reproducible or dosage-related increases in the frequency of 6-thioguanine resistant cells. There were no reproducible or dosage-related increases in sister chromatid exchanges in an in vitro test in CHO cells. An in vitro cytogenetics study in CHO cells showed no evidence for an increase in chromosomal aberrations on treatment with GA, either in the presence or absence of metabolic activation. In vivo, a mouse peripheral blood micronucleus test showed no increase in micronucleated polychromatophils at sampling times of 30, 48 and 72 h after acute gavage dosing with GA at 40, 80 and 125 mg kg−1 (corresponding to 25, 50 and 85% of the LD50). The absence of an in vivo clastogenic potential was confirmed by no increase in chromosomal aberrations in a rat bone marrow cytogenetics study with sampling at 12, 24 and 48 h after acute gavage dosing with GA (12.5, 30 or 60 mg kg−1 with males, and 7.5, 20 or 40 mg kg−1 with females). Thus, in this series of tests, GA produced genotoxic effects in vitro only in a bacterial reverse mutation assay with no evidence for in vivo genotoxicity. Copyright © 2002 John Wiley & Sons, Ltd.

Urinary 8-hydroxydeoxyguanosine and sister chromatid exchanges in patients with total hip replacements

Abstract: Ion release from metal implants has been suspected to increase the risk of genotoxic effects in patients wearing orthopedic metal devices In this study we used urinary 8-hydroxydeoxyguanosine (8-OHdG) as marker of oxidative DNA damage and the frequency of sister chromatid exchanges in lymphocytes to test a possible relationship between the concentrations of chromium or cobalt and the induction of cytogenetic modifications in 46 patients with total hip replacements A broad range of individual levels of metals has been observed in these patients: chromium in blood, 159-1411 microg/L; chromium in urine, 079-9380 microg/24 h; cobalt in blood, 077-3780 microg/L; cobalt in urine, 259-16694 microg/24 h By linear regression analysis, no significant correlation between urinary 8OHdG or sister chromatid exchange (SCE) and the concentrations of metals was found However, cobalt in blood as well as 8-OHdG in urine were higher in patients with implants 3-4 yr old as compared to patients with implants 1-2 yr old Smoking significantly increased the frequency of SCE Our data do not indicate a dependence of 8-OHdG in urine or SCE on the levels of chromium or cobalt in patients with total hip replacements

The Coprinus cinereus adherin Rad9 functions in Mre11-dependent DNA repair, meiotic sister-chromatid cohesion, and meiotic homolog pairing

Abstract: Mitotic sister-chromatid cohesion (SCC) is known to depend in part on conserved proteins called adherins, which although necessary for SCC are not themselves localized between sister chromatids. We have examined mitotic DNA-repair and meiotic chromosome behavior in the Coprinus cinereus adherin mutant rad9-1. Genetic pathway analysis established that Rad9 functions in an Mre11-dependent pathway of DNA repair. Using fluorescence in situ hybridization, we found that the rad9-1 mutant is defective in the establishment of meiotic homolog pairing at both interstitial and subtelomeric sites but in the maintenance of pairing at only interstitial loci. To determine the role of Rad9 in meiotic SCC, we hybridized nuclear spreads simultaneously with a homolog-specific probe and a probe that recognizes both members of a homologous pair. We found that Rad9 is required for wild-type levels of meiotic SCC, and that nuclei showing loss of cohesion were twice as likely also to fail at homolog pairing. To ask whether the contribution of Rad9 to homolog pairing is solely in the establishment of SCC, we examined a rad9-1;msh5-22 double mutant, in which premeiotic DNA replication is inhibited. The msh5-22 mutation partially suppressed the deleterious effects of the rad9-1 mutation on homolog pairing; however, pairing in the double mutant still was significantly lower than in the msh5-22 single mutant control. Because the role of Rad9 in homolog pairing is not obviated by the absence of a sister chromatid, we conclude that adherins have one or more early meiotic functions distinct from the establishment of cohesion.

Additive action of vitamins C and E against hydrocortisone-induced genotoxicity in human lymphocyte chromosomes.

Abstract: In earlier reports, hydrocortisone administration to human lymphocytes in culture was shown to cause chromosomal aberrations and increased sister chromatid exchanges. With a view to study the ameliorative action of some antioxidants against this effect, vitamins C and E were used separately and in combination along with hydrocortisone treatment, at different dosage and for different durations, on human lymphocyte cultures. The levels of chromosomal aberrations and sister chromatid exchanges were lowered, suggesting a protective role of vitamins against genotoxic damage. Administration of vitamins C and E combined appeared to be more effective in preventing chromosomal damage than separate administration, demonstrating the additive action of these vitamins against steroid-induced genotoxicity.

Acute wood or coal exposure with carbon monoxide intoxication induces sister chromatid exchange.

Abstract: Objective: The object of this study was to investigate the genotoxic effect of acute overexposure to combustion products originating from coal or wood stoves in patients presenting with acute carbon monoxide intoxication. Study Design: In a prospective study, we analyzed the frequency of sister chromatid exchange and the carboxyhemoglobin concentration in 20 consecutive patients without a history of smoking or drug use who had been treated in the Emergency Care Unit of Istanbul Medical Faculty due to acute carbon monoxide intoxication. All of these cases were domestic accidents due to dysfunctioning coal or wood stoves. The results were compared with a control group of 20 nonsmoking, nondrug-using healthy individuals matched for age, sex, and absence of other chemical exposure. Results: The mean sister chromatid exchange frequency per metaphase was significantly higher in the study group compared to the control group: 8.11±2.39 vs. 6.33±1.60 (p=0.008). We found that there was no positive correlation betwe...

Metabolite ratio of toluene-exposed rotogravure printing plant workers reflects individual mutagenic risk by sister chromatid exchanges.

Abstract: The study involved a group of 42 printing plant workers and a control group of 45 blood donors. At the working places, the ambient air-toluene concentration amounted from 141 to 328 mg/m(3). Sister chromatid exchanges (SCEs) were significantly elevated by three units in the exposed group. In this group, the concentration of urinary toluene metabolites was also considerably increased-hippuric acid was four times higher and the o-cresol and p-cresol fractions were twice as high. Results of toluene monitoring of ambient air- or blood-toluene concentrations did not show any relationships with individual SCE. While these SCE values revealed only a weak relationship with the corresponding hippuric acid data, a significant correlation with the cresols, which are known to be more genotoxic than hippuric acid, appeared in highly exposed workers. An attempt was made to consider the individual metabolic balance of toluene excretion products. For that reason individual cresol to hippuric acid ratios were calculated and related to corresponding SCE values. In all investigated subpopulations of the exposed group, this ratio correlated with SCE at a level of high significance. This strong interrelationship is a powerful argument for the genotoxic behavior of toluene. Furthermore, the individual metabolic balance, as a consequence of genetic polymorphism, should be considered in the discussion about genetic risk of toluene.