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• W2074080643 abstract "To investigate the ability of topotecan, a topoisomerase I-targeting anticancer drug, to induce dominant lethal mutations in male mouse germ cells, males were treated with single doses of 3, 6 and 12 mg/kg topotecan. Each male was mated at 4-day intervals to virgin females for a total of nine 4-day mating intervals. The two highest doses of topotecan are shown to be mutagenic in post-meiotic cells. The greatest effect occurred in those cells which were in the early-spermatid stage at the time of exposure. Mice treated with 12 mg/kg topotecan showed an additional peak of dominant lethal induction in mature sperm during the first 4-day matings after treatment. The mutagenic effects were directly correlated with free radicals accumulation as an obvious increase in the generation reactive oxygen species and 8-hydroxydeoxyguanosine was noted in animals treated with 6 and 12 mg/kg topotecan. Treatment of male mice with N-acetylcysteine, a free radical scavenger, significantly protected mice from topotecan-induce dominant lethality. Moreover, N-acetylcysteine had no antagonizing effect on topotecan-induce topoisomerase-I inhibition. Our study provides evidence that topotecan is a germ cell mutagen and its effect is more pronounced during the post-meiotic stages through a mechanism that may involves increases in DNA oxidative stress." @default.
• W2074080643 created "2016-06-24" @default.
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• W2074080643 date "2013-12-01" @default.
• W2074080643 modified "2023-10-17" @default.
• W2074080643 title "Germ cell mutagenicity of topoisomerase I inhibitor topotecan detected in the male mouse-dominant lethal study" @default.
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• W2074080643 doi "https://doi.org/10.1016/j.fct.2013.09.009" @default.
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