The mutagenic activity of -propiolactone in Saccharomyces cerevisiae.
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Biomedical subjects
Publications and source records attributed to D J Brusick.
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N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces cycloheximide-resistant mutations in Saccharomyces cerevisiae, but few, if any, resistant mutants are induced by the acridine mustard ICR-170. Cycloheximide sensitivity in yeast is associated with the ribosome, and treatment with the antibiotic at concentrations of 2 mug/ml results in complete inhibition of protein synthesis. Missense mutations induced by MNNG probably lead to the loss of cycloheximide binding sites on the ribosome, resulting in resistance to the antibiotic without altering the activity of the organelle in protein synthesis. ICR-170, however, induced primarily frameshift mutations that would alter ribosome structural integrity, resulting in cell death rather than resistance. ICR-170 and MNNG are both mutagenic in a system in which base-pair substitution and frameshift mutations can be detected. These results indicate that cycloheximide resistance in S. cerevisiae, like streptomycin and spectinomycin resistance in Escherichia coli, can be induced by base-pair substitution mutagens but not by frameshift mutagens such as ICR-170.
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Several tester strains of Salmonella typhimurium, TA-98, TA-100, TA-1535, and TA-1538; Escherichia coli, W3110 (pol A+) and p3438 (pol A-, repair deficient); and Saccharomyces cerevisiae, D3, D4, and D5 were tested for lethal and mutagenic events when exposed to elevated temperatures or to x-band, pulsed microwave radiation at various power densities. When compared to E. coli pol A+ under growing conditions, E. coli pol A- exhibited decreased cell growth when exposed to microwave radiation at power levels at or above 20 mW/cm2 as well as to temperature levels above 42 degrees C. All yeast and other bacterial strains showed cellular lethality at similar microwave intensities and elevated temperatures. When exposed to elevated temperatures in saline, both quiescent yeast and Salmonella strains exhibited lethal events. However, the Salmonella strains tested showed comparatively less induction of genetic events in the quiescent state compared to induction when the cell were actively growing in broth. These results demonstrate that elevated temperatures generated by microwave exposure could produce genetic events in microbial assay systems. If such systems are to be of value in examining the nonthermal genetic potential of microwave radiation, careful control over exposure conditions will be required to eliminate heat-induced genetic events.