DiPaolo J A, Casto B C
Natl Cancer Inst Monogr. 1978 May(48):245-57.
A well-documented rationale exists for the study of the induction of cancer at the cellular level. Transformation can be quantitated; its frequency follows a linear relationship with dose and is consistent with a "one-hit" phenomenon. Transformed colonies do produce transformed lines with attributes of neoplastic cells including the production of tumors; in vitro activity correlates with in vivo activity to provide evidence that chemically induced carcinogenesis can be studied in vitro. In vitro techniques utilizing mammalian cells in culture have made possible the rapid evaluation of carcinogenicity of agents in man's environment. Neoplastic transformation is inductive and not the result of the selection of preexisting tumor cells. The addition of a host-mediated step in the bioassay makes it possible to decrease the number of false negatives, which may result from the requirement for metabolic activation of the chemical. Thus the in vitro studies described have a high probability of providing practical methods for determining which chemicals in use have a potential of producing cancer. Furthermore, the nature of the cell-target insult interaction can be determined, as well as the chemical nature of the ultimate carcinogen, the degree to which any agent acts alone, be it a chemical, a virus, or irradiation, and the extent to which one agent interacts with another from the same or a different category of carcinogens. Sequential treatment involving chemicals, viruses, and radiation are important, since combinations of various agents may be responsible for an increased risk of cancer in laboratory animals and human populations. The use of multiple agents may also lead to different but specific new types of assays to use for surveillance of our environment for carcinogenic agents. Pretreatment of Syrian golden hamster embryo cells with either X-irradiation or methyl methanesulfonate, but not UV-irradiation, increases the frequency of chemical transformation as does posttreatment with caffeine. Most, if not all, chemical carcinogens will increase the sensitivity of hamster embryo cells to transformation by a carcinogenic simian adenovirus SA7. The enhancement of virus transformation is related to both the length of chemical treatment and the interval between chemical and viral addition. The mechanism of transformation enhancement by various agents has yet to be explained. They may affect a number of molecular processes or cause a modification of existing DNA and thus provide an explanation for carcinogenesis; in fact, in some systems some of these agents may also show mutagenic activity and produce chromosomal aberrations, However, although DNA is the critical site for a mutagen, the critical target(s) of chemical carcinogens is still unknown.
在细胞水平上研究癌症诱导作用存在充分的理论依据。转化可以进行定量；其频率与剂量呈线性关系，并且符合“一次打击”现象。转化后的集落确实能产生具有肿瘤细胞特性的转化细胞系，包括肿瘤的产生；体外活性与体内活性相关，这为在体外研究化学诱导的致癌作用提供了证据。利用培养的哺乳动物细胞的体外技术使得快速评估人类环境中化学物质的致癌性成为可能。肿瘤转化是诱导性的，而不是预先存在的肿瘤细胞选择的结果。在生物测定中增加宿主介导步骤可以减少假阴性的数量，假阴性可能是由于化学物质需要代谢激活所致。因此，所述的体外研究很有可能提供实用方法，以确定正在使用的哪些化学物质具有致癌潜力。此外，可以确定细胞 - 靶标损伤相互作用的性质，以及最终致癌物的化学性质、任何一种物质单独起作用的程度（无论是化学物质、病毒还是辐射），以及一种物质与同一类或不同类致癌物中的另一种物质相互作用的程度。涉及化学物质、病毒和辐射的序贯处理很重要，因为各种物质的组合可能导致实验动物和人类群体患癌风险增加。使用多种物质还可能导致不同但特定的新型检测方法，用于监测我们环境中的致癌物质。用X射线或甲磺酸甲酯（但不是紫外线）预处理叙利亚金黄地鼠胚胎细胞，与用咖啡因后处理一样，会增加化学转化的频率。大多数（如果不是全部）化学致癌物会增加地鼠胚胎细胞对致癌性猿猴腺病毒SA7转化的敏感性。病毒转化的增强与化学处理的持续时间以及化学物质添加与病毒添加之间的间隔有关。各种物质增强转化的机制尚待解释。它们可能影响许多分子过程或导致现有DNA的修饰，从而为致癌作用提供解释；事实上，在某些系统中，其中一些物质也可能表现出诱变活性并产生染色体畸变。然而，虽然DNA是诱变剂的关键位点，但化学致癌物的关键靶标仍然未知。
