Albert R E
Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH 45267-0056, USA.
Environ Health Perspect. 1997 Sep;105(9):940-8. doi: 10.1289/ehp.97105940.
Chemicals that were bioassayed by the National Toxicology Program (NTP) and that also produce allergic dermatitis (ACD) in humans were evaluated for their tumorigenic characteristics. The impetus for the study was that most contact sensitizers, i.e., those that produce ACD, and genotoxic carcinogens are chemically similar in that they are electrophilic, thereby producing adducts on macromolecules including protein and DNA. This similarity in chemical behavior suggests that many contact sensitizers might be environmental carcinogens. All of the published NTP bioassays by early 1996 that had both genotoxicity and carcinogenicity studies were included in this analysis. The NTP chemicals had been chosen for bioassay without regard to their ability to produce ACD. Of the 209 chemicals that were bioassayed, there were 36 (17%) that were known to be human contact sensitizers; about half of these were positive on tumor bioassays. The contact sensitizers differed from the NTP sample as a whole by having a proportionately larger number of nongenotoxic chemicals by the Ames Salmonella assay, presumably because more of them were selected on the basis of widespread usage rather than structural resemblance to known carcinogens. Compared to the nongenotoxic chemicals, the genotoxics were stronger carcinogens in that they had a higher incidence of positive tumor bioassays, with twice the number of organs in which tumors were induced. The nongenotoxic chemicals had a preference for tumor induction in parenchymal tissues in contrast to epithelial tissues. The contact sensitizers showed essentially the same characteristics as the whole NTP sample when stratified according to genotoxicity. Judging by the chemicals that were chosen primarily for their widespread use rather than for their structural resemblance to carcinogens, the addition of a test for contact sensitization to the Ames test as a screening tool would increase the tumorigenic detection efficiency by about 40% because of the nongenotoxic tumorigens. A ballpark estimate suggests that there could be several thousand contact sensitizers for humans in commercial use that are rodent tumorigens.
美国国家毒理学计划（NTP）进行过生物测定且会在人体引发过敏性皮炎（ACD）的化学物质，对其致癌特性进行了评估。开展这项研究的动机在于，大多数接触性致敏原，即那些引发ACD的物质，与遗传毒性致癌物在化学性质上相似，因为它们具有亲电性，从而会在包括蛋白质和DNA在内的大分子上形成加合物。这种化学行为上的相似性表明，许多接触性致敏原可能是环境致癌物。本次分析纳入了1996年初NTP已发表的所有同时进行了遗传毒性和致癌性研究的生物测定。NTP选择用于生物测定的化学物质时并未考虑其引发ACD的能力。在接受生物测定的209种化学物质中，有36种（17%）已知是人类接触性致敏原；其中约一半在肿瘤生物测定中呈阳性。接触性致敏原与NTP样本整体的不同之处在于，通过艾姆斯沙门氏菌试验，其非遗传毒性化学物质的比例相对较大，据推测这是因为其中更多物质是基于广泛使用而被选择的，而非与已知致癌物的结构相似性。与非遗传毒性化学物质相比，遗传毒性化学物质是更强的致癌物，因为它们在肿瘤生物测定中呈阳性的发生率更高，诱导肿瘤的器官数量是前者的两倍。非遗传毒性化学物质更倾向于在实质组织而非上皮组织中诱导肿瘤。当根据遗传毒性进行分层时，接触性致敏原表现出与整个NTP样本基本相同的特征。从主要因其广泛使用而非与致癌物的结构相似性而被选择的化学物质来看，在艾姆斯试验中增加一项接触性致敏试验作为筛选工具，由于非遗传毒性致癌物的存在，将使致癌检测效率提高约40%。大致估计表明，商业用途中可能有数千种对人类有接触性致敏作用的物质是啮齿动物致癌物。
