The relationship between reaction kinetics and mutagenic action of monofunctional alkylating agents in higher eukaryotic systems: IV. The effects of the excision-defective mei-9L1 and mus(2)201D1 mutants on alkylation-induced genetic damage in Drosophila

摘要: Abstract Repair-defective mutants of Drosophila melanogaster which identify two major DNA excision repair loci have been examined for their effects on alkylation-induced mutagenesis using the sex-linked recessive lethal assay as a measure genotoxic endpoint. The alkylating agents (AAs) chosen comparative analysis were selected basis reaction kinetics with and included MMS, EMS, MNU, DMN, ENU, DEN ENNG. Repair-proficient males treated AAs mated either excision-defective mei-9 L1 or mus(2)201 D1 females appropriate excision-proficient control females. results present work suggest that qualitative quantitative relationship exists between nature extent chemical modification induction genetic alterations. presence mutant can enhance frequency mutation (hypermutability) this hypermutability be correlated Swain-Scott constant S specific such N 1 character alkylation increases, difference in response repair-deficient repair-proficient decreases. order relative to is MMS > MNU DMN = EMS iPMS ENU When percentage mutations induced are plotted against those determined females, straight lines different slopes obtained. These mei -9 / + indices are: 7.6, 5.4, 2.4, 2.4 ENNG 1. An identical similar obtained mus (2)201 mutants: MMS(7.3) MNU(5.4) EMS(2.0) ENU(1.1). Thus, absence function has significant effect production by efficient N-atoms but no measurable influence most O-atoms DNA. possible these adducts discussed relation alkylated In another series experiments, was studied males, comparing vs. activity Berlin K (control). Although experiments suggested existence postmeiotic cells during spermatogenesis, comparisons could made. inherent problem approach, mutagen treatment genotypes, factors entirely unrelated repair, e.g., differences metabolism, may outcome comparison. Utilization low dosage did out measurably improve sensitivity lethals. Because allele not characterized biochemically, we cannot determine at whether deficiency, per se, will lead notable shifts lowest effective concentrations (LECs) ‘leaky’ providing some wild-type doses. Nevertheless, ‘high-exposure-level’ strong reference mutagens indicative situation relevant activities aspect should given special attention considerations dealing use repair-defective alleles toxicology testing.