Germline mutation induction at mouse repeat DNA loci by chemical mutagens.
Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of male mice exposed to two monofunctional alkylating agents, ethylnitrosourea (ENU) and isopropyl methanesulfonate (iPMS), and a topoisomerase II inhibitor, etoposide. Pre-meiotic exposure to the alkylating agents resulted in a highly significant increase in ESTR mutation rate, but did not alter post-meiotically exposed cells. Pre-meiotic mutation induction by ENU and iPMS was linear within the interval of doses from 12.5 to 25mg/kg and reached a plateau at higher concentrations. Paternal exposure to etoposide resulted in ESTR mutation induction at meiotic stages but did not affect post- or pre-meiotic cells. The pattern of ESTR mutation induction after pre-meiotic and meiotic exposure to chemical mutagens was similar to that previously obtained by various traditional approaches for monitoring germline mutation in mice. The results of this study show that ESTR loci provide a new efficient experimental system for monitoring the genetic effects of chemical mutagens, capable of detecting increases in mutation rates at low doses of exposure.
Vilariño-Güell
Carles
C
Department of Genetics, University of Leicester, UK.
Smith
Andrew G
AG
Dubrova
Yuri E
YE
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D003434:Crossing Over, Genetic / Q000187:drug effects / Q000235:genetics*; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005038:Ethylnitrosourea / Q000633:toxicity*; D005047:Etoposide / Q000633:toxicity; D005260:Female; D018095:Germ-Line Mutation / Q000187:drug effects*; D008297:Male; D008540:Meiosis / Q000187:drug effects* / Q000235:genetics*; D008698:Mesylates / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013091:Spermatogenesis / Q000187:drug effects* / Q000235:genetics; D020080:Tandem Repeat Sequences; D059005:Topoisomerase II Inhibitors
D000477:Alkylating Agents; D000972:Antineoplastic Agents, Phytogenic; D008698:Mesylates; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D004247:DNA; D005038:Ethylnitrosourea; C002531:isopropylmethanesulfonate