Showing papers in "Mutation Research\/environmental Mutagenesis and Related Subjects in 1975"

Procedures used in the induction of mitotic recombination and mutation in the yeast Saccharomyces cerevisiae.

Abstract: Techniques are described for the use of various yeast strains to detect the induction of (1) mitotic crossing-over, (2) mitotic gene conversion, (3) forward mutation and (4) reverse mutation. The technique for the detection of mitotic crossing over is based on a diploid that carries two different alleles of the gene locus ade2. These alleles differ in their extent of colony pigmentation engendered on low-adenine media, and they complement each other to the effect that the diploid is white. Mitotic crossing over results in the formation of twin-sectored colonies with a red and a pink sector. The technique for the detection of mitotic gene conversion is based on the use of a heteroallelic diploid carrying two non-complementing alleles that cause a nutritional requirement. Mitotic gene conversion leads to the restoration of intact and dominant wild-type alleles that alleviate the nutritional requirement so that convertant cells can be selected on a minimal medium. The forward mutation technique is based on the use of a haploid strain with a defect in the ade2-gene locus which causes the formation of red colonies. Induction of forward mutation in a number of other loci prevents the accumulation of this red pigment so that induction of mutation can be detected by the formation of pink and white colonies. The reverse mutation technique is based on the restoration or compensation of a mutational defect causing a growth requirement. Mutants can be selected for a minimal medium.

Root tips of Vicia faba for the study of the induction of chromosomal aberrations

Abstract: One of the oldest, simplest and least expensive methods for studying the induction of chromosomal aberrations utilizes plant root tips as experimental material. The merits of this material were already realized by radiobiologists in the 1930's. The root tip technique is particularly well suited for the study of chemically induced aberrations. However, the method is no exception to the rule that reliable and valuable results can only be obtained when the experiments are correctly and carefully carried out. This requires a good knowledge of the material and its reactions towards different types of treatment.

Mutagenicity of sodium hypochlorite for Salmonella typhimurium.

Abstract: Sodium hypochlorite, a standard household item, induces base-substitution mutations in Salmonella typhimurium. Because of its potent bactericidal effect the mutagenicity of hypochlorite could best be demonstrated by short-term exposure to this chemical followed by the addition of ascorbic acid to decompose the hypochlorite.

Mutagen screening with bacteria: niridazole and nitrofurans.

Abstract: The mutagenic activity of nitrofuran derivatives and of niridazole is easily demonstrated by spot tests using E. coli WP2 and its uvrA derivative but not by spot tests using the S. typhimurium strains developed by Ames. Quantitative tests show that S. typhimurium TA 1538(but not TA 1535, -36 or -37) is weakly induced to revert by niridazole. However, the maximum yield of revertants is well below that obtained with E. coli WP2 uvrA. None of the S. typhimurium strains respond to the three nitrofurans tested even in quantitative tests. The S. typhimurium strains contain the reductase required for metabolic activation of the nitrofurans and treatment of a uvr+ S. typhimurium strain with niridazole or with nitrofurazone causes single-strand breaks in DNA.

Quantitative relationship between carcinogenecity and mutagenicity of polyaromatic hydrocarbons in Salmonnella typhimurium mutants

Abstract: Mutagenic activities of various polyaromatic hydrocarbons (PAHs) in air pollutants, which are different in carcinogenic activities from each other, were examined with a set of four strains of Salmonella typhimurium (TA1535 series; deep rough strains without excision repair). All the compounds tested were converted to frameshift mutagens when they were metabolized by rat liver homogenate. There was a clear quantitative correlation between carcinogenicity and mutagenicity of PAHs tested in strain TA1538 using the rat liver enzyme induced with both dibenz(a,h)-anthracene and phenobarbital. On the other hand, such a correlation was not obvious in strain TA1537.

The effect of methylxanthines on chromosomes of human lymphocytes in culture

Abstract: The effect of caffeine (1,3,7-trimethylxanthine), theophylline (1,3-dimethyl-xanthine), theobromine (3,7-dimethylxanthine), paraxanthine (1,7-dimethylxanthine) 1-methylxanthine, 3-methylxanthine, and 7-methylxanthine added at the 48th h on the chromosomes of human lymphocytes in 72-h cultures has been investigated. Caffeine and the dimethylxanthines cause breakage at 750 μg/ml, with caffeine the most, and paraxanthine the least clastogenic. 1-methylxanthine and dimethylxanthines with a methyl group in the 1-position are the most effctive in depressing mitotic indices. No chromosome damage was exhibited by the monomethylxanthines.

In vitro metabolic activation of chemical mutagens. II. The relationships among mutagen formation, metabolism and carcinogenicity for dimethylnitrosamine and diethylnitrosamine in the livers, kidneys and lungs of BALB/cJ, C57BL/6J and RF/J mice.

Abstract: The metabolic activation of dimethylnitrosamine (DMNA) and diethylnitrosamine (DENA) to mutagenic intermediates was studied using an in vitro genetic assay which measured the relative concentration and rate of formation of the active intermediates. Microsomal preparations from the livers, lungs and kidneys of BALB/cJ, C57BL/6J and RF/J male mice were compared for their ability to activate the two carcinogens to mutagens. It was demonstrated that quantitative differences in activation could be detected between organs of the three strains and that different organs have characteristic activation kinetics. Activation kinetics for microsomal metabolism of DMNA by liver, lung and kidney tissues of male and female C57BL/6J mice were also compared. Except for the female kidney preparations which appeared to lack the ability to activate DMNA and DENA, the activation properties for the male and female organs were quite similar. The results from this investigation tend to support the hypothesis that a single activated metabolite of DMNA is responsible for both its carcinogenic and mutagenic properties.

Interactive mutagenicity of sodium nitrite, dimethylamine, methylurea and ethylurea.

Abstract: Groups of mice were treated per os with sodium nitrate either alone or in combination with nitrosatable amino compounds and tested in the most mediated assay When mice were treated with sodium nitrate in combination with demethylamine a small(4-fold) but significant increase in mutant frequency (MF) was observed Ethylurea or methylurea in combination with sodium nitrate induced 10- or 850-fold increases in MF, respectively The response to methylurea was dose-dependent with a 6- and 30- fold increase in MF at 54 and 115 mg/kg NaNO 2 and a 6-fold increase at 108 mg/kg methylurea That this response reflected gastric nitrosation was shown by the disappearance of the response if NaNO 2 administration preceded methylurea treatment by 10 min High MF's were observed if NaNO 2 was administered 10 or 20 min after methylurea

Acute cytogenetic effect of 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF-2, a food preservative) on rat bone marrow cells in vivo

Abstract: The cytogenetic effects of 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF-2), a food preservative used in Japan, on rat bone marrow cells in vivo were studied. The aberrant metaphase cells in the bone marrow increased and reached the peak level 6 h after intraperitoneal injection of 240 mg/kg body weight of AF-2 and returned to the normal level within 24 h. A dose-response relationship was obtained using 4–240 mg/kg of AF-2. Chromosome aberrations were also induced after oral administration of 30–240 mg/kg. The aberrations were mostly chromatid breaks and the distribution among and within chromosomes was similar to those induced by a carcinogen, 7,12-dimethylbenz( a )anthracene (DMBA). The present results provide the first evidence of in vivo cytogenetic effects of AF-2 on mammalian cells and, together with the evidence of mutagenicity already proved in other organisms, warn of the possible genetic hazards to cells exposed to this compound.

The mutagenic action of nitroimidazoles. II. Effects of 2-nitroimidazoles.

Abstract: The 2-nitroimidazoles Ro-71051 (N-benzyl-2-nitro-1-imidazole-acetamide) and Ro-5-9963 (3(2-nitro-1-imidazolyl)-1,2-propanediol) increased the mutation rate of a Klebsiella pneumoniae mutant to streptomycin-resistance including streptomycin-dependence in Luria and Delbruck's fluctuation test in concentrations of 0.05-1 mM and 0.02-0.2 mM respectively. The 2-nitroimidazole, azomycin, (Ro-5-9129/001) failed to increase the mutation rate. The results are compared to those obtained with the 5-nitroimidazoles methronidazoles metronidazole, nimorazole and dimetridazole, which caused a degree of increase similar to Ro-7-1051 and Ro-59963.

Microsomal activation to mutagens of antischistosomal methyl thioxanthenones and initial tests on a possibly non-mutagenic analogue.

Abstract: Five methylthioxanthenone and methylbenzothiopyranoindazole analogues, including lucanthone (Miracil D), are non-mutagenic for Salmonella typhimurium but are activated to mutagens by a rat liver microsome preparation. Hydroxymethyl analogues, includinng hycanthone )Etrenol), are mutagenic in the absebce of microsomes. It seems reasonable to assume that the hydroxymethyl derivatives are the more proximal mutagens and that Salmonella is unable to carry out the hydroxylation necessary for mutagen activation. During the past 24 years, several million patients with schistosomiasis have been treated with lucanthone, and in recent years about 700 000 persons with hycanthone. The possible long-term deleterious effects of these agents for man even now remain to be determined. Our studies indicate that particular modifications in the structure of thioxanthenones drastically alter their mutagenicity. One apparently non-mutagenic thioxanthenone has been found. A number of the less mutagenic compounds also exhibit decreased acute toxicity in the mouse while retaining appreciable antischistosomal activity, suggesting that genetic and schistosomicidal activities may be dissociated from each other.

Lack of induction of dominant lethals in mice by orally administered AF-2.

Abstract: In a series of toxicity tests, male mice of three inbred strains were exposed to several doses of orally administered furylfuramide (AF-2). Subsequent to these tests the effects of AF-2, as measured by induced dominant lethals, were tested in strain DBA/2J mice. AF-2 at the doses used in this study was relatively non-toxic to the strains of mice tested. No indication of AF-2 induced dominant lethality was observed.

The effects of lead on algae II. Mutagenesis experiments on Platymonas subcordiformis (Chlorophyta: volvocales)

Abstract: Under conditions in which two known mutagenic agents, ultraviolet irradiation and nitrosoguanidine (MNG), induced high proportions of mutations (chiefly affecting growth rate and colony form), PbCl2 produced no appreciable increase in the incidence of such mutant types above the spontaneous frequency in Platymonas subcordiformis.

Cytological studies on onion root-tip cells treated with water-soluble extract of tobacco smoke condensate from commercial cigarettes.

Abstract: The effect of water-soluble extract of tobacco smoke condensate (TSC) from two commercially available cigarettes with different types of filters was studied on the cytology of root-tips cells of onion ( Allium cepa ). One of the cigarettes had a 2-cm cellulose acetate filter, and the other had a filter comprised of 1 cm of cellulose acetate and 1 cm of activated charcoal. TSC from these cigarettes induced mitotic abnormalities. To investigate whether these two commercial filters could retain cigarette smoke component(s) responsible for mitotic irregularites, the cigaretts were defiltered,and TSC was prepared and tested on the young roots of onion. Observations revealed that the cytological effect of TSC from defiltered cigarettes was not significantly different from the effect of TSC from cigarettes with filters. Thus, the filters utilized in these cigarettes do not retain compound(s) responsible for mitotic irregularities in the root-tip cells of onion. With increasing concentrations (0.01% to 0.1%) of TSC from cigarettes 3ith filters and defiltered, percent mitotic abnormalities increased. These abnormalities included scattering, stickiness, lagging, condensation, and breaking of chromosomes during metaphase. Bridging and lagging of chromosomes were observed during anaphase.