Biomaterial Database

A rapid somatic genotoxicity assay in Drosophila melanogaster using multiple mutant mutagen-sensitive (mus) strains. 1992

D S Henderson, and T A Grigliatti

Department of Zoology, University of British Columbia, Vancouver, Canada.

Mutagen-sensitive (mus) mutations in Drosophila melanogaster render developing flies hypersensitive to the lethal effects of DNA-damaging agents. In principle, multiply mutant mus strains might then serve as sensitive in vivo indicators of a wide range of mutagens and genotoxic carcinogens. As a first step to evaluate that potential we characterized interactions between mus mutations in eight double mutants containing combinations of the second chromosomal mutations mus201D1, mus205B1, mus208B1, mus210B1 and mus211B1. We found that (i) all double mutants are fully viable in the absence of mutagen exposure, (ii) mus205B1 is epistatic to any other mus mutation with respect to methyl methanesulfonate (MMS) sensitivity, and (iii) in double mutants carrying any combination of mus201D1, mus210B1 or mus211B1, MMS sensitivity is increased in a synergistic manner. Based on those results, and on mutagen cross-sensitivity data of single mutants generated in previous studies, we constructed two triple mutant mus strains for use as testers in a simple genotoxicity assay. That assay measures the survival of DNA repair-deficient mus homozygotes relative to their repair-proficient heterozygous siblings. Those two classes of fly are easily distinguished from one another by their phenotypic markers. In addition, the heterozygotes serve as a relatively mutagen-insensitive internal control in all test vials. One tester strain (mus208B1 mus210B1 mus211B2) identified 11 of 12 chemical carcinogens as genotoxic (benzo[a]pyrene, cyclophosphamide, 1,2,3,4-diepoxybutane, diethylnitrosamine, dimethylnitrosamine, ethyl methanesulfonate, formaldehyde, hexamethylphosphoramide, methyl methanesulfonate, methylnitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine). Safrole and two noncarcinogens (benzo[e]pyrene and caprolactam) tested as nongenotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008741	Methyl Methanesulfonate	An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.	Methylmethane Sulfonate,Dimethylsulfonate,Mesilate, Methyl,Methyl Mesylate,Methyl Methylenesulfonate,Methylmesilate,Mesylate, Methyl,Methanesulfonate, Methyl,Methyl Mesilate
D009152	Mutagenicity Tests	Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.	Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D009153	Mutagens	Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.	Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D004331	Drosophila melanogaster	A species of fruit fly frequently used in genetics because of the large size of its chromosomes.	D. melanogaster,Drosophila melanogasters,melanogaster, Drosophila
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D005069	Evaluation Studies as Topic	Works about studies that determine the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies.	Critique,Evaluation Indexes,Evaluation Methodology,Evaluation Report,Evaluation Research,Methodology, Evaluation,Pre-Post Tests,Qualitative Evaluation,Quantitative Evaluation,Theoretical Effectiveness,Use-Effectiveness,Critiques,Effectiveness, Theoretical,Evaluation Methodologies,Evaluation Reports,Evaluation, Qualitative,Evaluation, Quantitative,Evaluations, Qualitative,Evaluations, Quantitative,Indexes, Evaluation,Methodologies, Evaluation,Pre Post Tests,Pre-Post Test,Qualitative Evaluations,Quantitative Evaluations,Report, Evaluation,Reports, Evaluation,Research, Evaluation,Test, Pre-Post,Tests, Pre-Post,Use Effectiveness