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首页> 外文期刊>Mutation Research: International Journal on Mutagenesis, Chromosome Breakage and Related Subjects >Induction of specific-locus and dominant lethal mutations in male mice by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).
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Induction of specific-locus and dominant lethal mutations in male mice by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).

机译：1,3-双（2-氯乙基）-1-亚硝基脲（BCNU）和1-（2-氯乙基）-3-环己基-1-亚硝基脲（CCNU）诱导雄性小鼠的特定基因座和显性致死突变。

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摘要

1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) induced dominant lethal and specific-locus mutations in male mice. For both compounds the germ cell stage sensitive to the induction of dominant lethal mutations was dose dependent. A dose of 5 mg BCNU per kg b.wt. induced dominant lethal mutations primarily in spermatocytes, whereas higher doses of BCNU induced dominant lethals in spermatids and spermatocytes. Following doses of 5 and 10 mg CCNU per kg b.wt. dominant lethals were induced in spermatids and spermatocytes similar to the results for higher doses of BCNU. Higher dose exposure to BCNU and CCNU was associated with dominant lethals expressed as pre-implantation loss (reduction in total number of implants). In addition, higher doses of CCNU showed a cytotoxic effect in differentiating spermatogonia. Both compounds induced specific-locus mutations in post-spermatogonial germ cell stages of mice. However, CCNU increased also the specific-locus mutation frequency in spermatogonia in two out of three experiments. We conclude in analogy with criteria developed by IARC, that BCNU and CCNU are potential human mutagens.
机译：1,3-双（2-氯乙基）-1-亚硝基脲（BCNU）和1-（2-氯乙基）-3-环己基-1-亚硝基脲（CCNU）诱导雄性小鼠的致命性和特定基因座突变。对于这两种化合物，对显性致死突变的诱导敏感的生殖细胞阶段是剂量依赖性的。每公斤体重5毫克BCNU剂量。诱导的主要致死性突变主要在精母细胞中，而更高剂量的BCNU诱导的精子和精子细胞的主要致死性突变。以下剂量为每公斤体重5和10毫克CCNU。与较高剂量的BCNU的结果相似，精子和精母细胞中的显性致死率被诱导。较高剂量的BCNU和CCNU暴露与显着的致死率相关，表现为植入前损失（植入物总数减少）。另外，较高剂量的CCNU在分化精原细胞中显示出细胞毒性作用。两种化合物均在小鼠精原细胞后生殖细胞阶段诱导特异性基因座突变。然而，在三分之二的实验中，CCNU也增加了精原细胞中特定基因座突变的频率。与IARC制定的标准类似，我们得出结论，BCNU和CCNU是潜在的人类诱变剂。

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