Bartsch H, Malaveille C, Tomatis L, Brun G, Dodet B, Terracini B
IARC Sci Publ. 1982(41):525-32.
The quantitative relationship between carcinogenicity in rodents and mutagenicity in S. typhimurium was examined using 10 monofunctional alkylating agents, including N-nitrosamides, alkylmethane sulfonates and epoxides. The compounds were assayed for mutagenicity in two S. typhimurium strains (TA1535, TA100) and in plate and liquid assays. Mutagenic activity was compared with alkylating activity, half-life (solvolysis constant) and carcinogenic activity in rodents (TD50). No correlations between these variables were found. However, there was a good positive relationship between the TD50 values of the carcinogens and the initial ratios of N-7-alkylguanine to 0(6)-alkylguanine formed after reaction with double-stranded DNA in vitro (r = 0.88, p less than 0.01; n = 9). From these results, it is concluded that the N-7/0(6)-alkylguanine ratio is quantitatively related to the carcinogenic activity for this class of compounds and it may therefore be used to predict the carcinogenic potency of new compounds within this class.
使用10种单功能烷基化剂（包括N - 亚硝酰胺、烷基甲烷磺酸盐和环氧化物）研究了啮齿动物致癌性与鼠伤寒沙门氏菌致突变性之间的定量关系。在两种鼠伤寒沙门氏菌菌株（TA1535、TA100）中以及平板和液体试验中对这些化合物进行了致突变性测定。将致突变活性与烷基化活性、半衰期（溶剂解常数）以及啮齿动物中的致癌活性（TD50）进行了比较。未发现这些变量之间存在相关性。然而，致癌物的TD50值与体外与双链DNA反应后形成的N - 7 - 烷基鸟嘌呤与O(6)-烷基鸟嘌呤的初始比率之间存在良好的正相关关系（r = 0.88，p小于0.01；n = 9）。从这些结果可以得出结论，N - 7/O(6)-烷基鸟嘌呤比率与这类化合物的致癌活性在数量上相关，因此它可用于预测这类新化合物的致癌潜力。
