Galli A, Schiestl R H
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.
Mutat Res. 1996 Oct 1;370(3-4):209-21. doi: 10.1016/s0165-1218(96)00078-x.
A wide variety of carcinogens including Ames assay (Salmonella) positive as well as Salmonella-negative carcinogens induce intrachromosomal recombination (DEL recombination) in strain RS112 of Saccharomyces cerevisiae. It has been previously shown that the Salmonella-positive carcinogens ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS) and 4-nitroquinoline-N-oxide (4-NQO) and the Salmonella-negative carcinogens safrole, benzene, thiourea, carbon tetrachloride and urethane induce DEL recombination in G2-arrested yeast cells. DEL recombination is preferentially induced by safrole, benzene and carbon tetrachloride in G2-arrested cells which might be explained by preferential induction of unequal sister chromatid recombination leading to deletions. To test this, cells of strain RS112 were arrested in the G1 phase of the cell cycle, exposed to these carcinogens and the frequencies of DEL and interchromosomal recombination (ICR) were determined. EMS, MMS and 4-NQO induced DEL recombination and ICR in G1-arrested cells with a linear dose-response curve. In contrast, the Salmonella-negative carcinogens safrole, benzene, carbon tetrachloride, thiourea and urethane induced DEL recombination and ICR with a threshold below which no significant increase was seen and only at already cytotoxic doses. EMS, MMS and 4-NQO were more recombinagenic in previous experiments with growing cells than in G1-arrested cells. On the other hand, safrole, benzene and carbon tetrachloride were more recombinagenic in G1-arrested than in growing cells. Thus, inducibility of DEL recombination in G1-arrested cells parallels inducibility in G2-arrested cells making it less likely that sister chromatid recombination events might be involved. These data are discussed in terms of the mechanism of induced DEL recombination and the possible biological activities of these carcinogens.
多种致癌物，包括艾姆斯试验（沙门氏菌）呈阳性的致癌物以及沙门氏菌阴性致癌物，均可在酿酒酵母RS112菌株中诱导染色体内重组（DEL重组）。先前已经表明，沙门氏菌阳性致癌物甲磺酸乙酯（EMS）、甲磺酸甲酯（MMS）和4-硝基喹啉-N-氧化物（4-NQO）以及沙门氏菌阴性致癌物黄樟素、苯、硫脲、四氯化碳和尿烷可在G2期停滞的酵母细胞中诱导DEL重组。在G2期停滞的细胞中，黄樟素、苯和四氯化碳优先诱导DEL重组，这可能是由于不等姐妹染色单体重组的优先诱导导致缺失所致。为了验证这一点，将RS112菌株的细胞停滞在细胞周期的G1期，使其暴露于这些致癌物中，并测定DEL和染色体间重组（ICR）的频率。EMS、MMS和4-NQO在G1期停滞的细胞中诱导DEL重组和ICR，呈线性剂量反应曲线。相比之下，沙门氏菌阴性致癌物黄樟素、苯、四氯化碳、硫脲和尿烷诱导DEL重组和ICR有一个阈值，低于该阈值未见显著增加，且仅在已经具有细胞毒性的剂量下才会出现。在先前对生长细胞的实验中，EMS、MMS和4-NQO比在G1期停滞的细胞中更具重组活性。另一方面，黄樟素、苯和四氯化碳在G1期停滞的细胞中比在生长细胞中更具重组活性。因此，G1期停滞细胞中DEL重组的诱导性与G2期停滞细胞中的诱导性相似，这使得姐妹染色单体重组事件参与其中的可能性较小。本文从诱导DEL重组的机制以及这些致癌物可能的生物学活性方面对这些数据进行了讨论。
