Ashby J, Lefevre P A, Styles J A, Charlesworth J, Paton D
Mutat Res. 1982 Mar;93(1):67-81. doi: 10.1016/0027-5107(82)90126-9.
8 derivatives of the rodent liver carcinogen 4-dimethylaminoazobenzene (DAB), all of known carcinogenicity in rodents, have been evaluated in the 3 major variants of the Salmonella mutation assay; the standard plate test of Ames et al., the pre-incubation assay of Yahagi et al. and the fluctuation assay of Gatehouse. Although 4 of these chemicals were reported to be non-carcinogenic, and 4 to be of greater carcinogenic potency than DAB, each was mutagenic in a least 2 of the assays. Further, no quantitative correlation between carcinogenic and mutagenic potency was evident in any of the assay employed. The parent carcinogen DAB, 5-dimethylaminophenylazoindazole (a non-carcinogenic bacterial mutagen) and 6-dimethylaminophenylazobenzthiazole (a carcinogenic bacterial mutagen) were administered to rats via intraperitoneal injection, followed, 26 h later, by a sub-acute dose of [14C] dimethylnitrosamine. The histopathological condition of the livers of the treated animals was assessed together with a determination of the extent and nature of methylation by DMN of the DNA in the livers according to the method of O'Connor. Disturbances in both the pathological and DNA-related parameters were observed for the 2 carcinogens while control levels were seen for the non-carcinogen. Within this context the value of short-term assays conducted in vivo is discussed, especially their potential to identify potent mammalian carcinogens from among a collection of structurally related bacterial mutagens.
已在沙门氏菌突变试验的3种主要变体中对啮齿动物肝脏致癌物4-二甲基氨基偶氮苯(DAB)的8种衍生物进行了评估,这些衍生物在啮齿动物中的致癌性均为已知;这3种变体分别是艾姆斯等人的标准平板试验、矢萩等人的预培养试验以及盖特豪斯的波动试验。尽管据报道这些化学物质中有4种无致癌性,4种的致癌效力比DAB更强,但每种物质至少在2种试验中具有致突变性。此外,在所采用的任何一种试验中,致癌效力与致突变效力之间均未表现出明显的定量相关性。通过腹腔注射将母体致癌物DAB、5-二甲基氨基苯基偶氮吲唑(一种无致癌性的细菌诱变剂)和6-二甲基氨基苯基偶氮噻唑(一种致癌性细菌诱变剂)给予大鼠,26小时后再给予亚急性剂量的[14C]二甲基亚硝胺。根据奥康纳的方法,对处理过的动物肝脏的组织病理学状况进行评估,并测定肝脏中DNA被二甲基亚硝胺甲基化的程度和性质。观察到2种致癌物在病理学参数和与DNA相关的参数方面均出现紊乱,而未观察到非致癌物出现此类情况。在此背景下,讨论了体内短期试验的价值,特别是其从一系列结构相关的细菌诱变剂中识别强效哺乳动物致癌物的潜力。