Ashman L K, Murray A W, Cook M G, Kotlarski I
Carcinogenesis. 1982;3(1):99-102. doi: 10.1093/carcin/3.1.99.
Strains of laboratory mice vary markedly in their susceptibility to two-stage skin carcinogenesis using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiating carcinogen and croton oil as promoter. This study has been undertaken in order to clarify the basis of the strain differences. LACA mice were used as the susceptible strain and BALB/c mice as the resistant strain. DMBA was a more effective complete carcinogen in LACA mice than in BALB/c mice. However, dose-response studies with respect to DMBA in the two strains in two-stage carcinogenesis suggested that metabolic activation of DMBA to the active carcinogen was not limiting in the resistant strain. The observed strain differences in response to DMBA in one and two stage carcinogenesis may reflect the ability of DMBA to also act as a promoter in the two strains. The possibility that the strains vary in their ability to repair damaged DNA has, however, not been eliminated. Unlike polycyclic aromatic hydrocarbon carcinogens such as DMBA, phorbol ester promoters (the active components in croton oil) do not appear to require metabolic activation. However, they are degraded and inactivated by epidermal and other cells. Experiments in which the dose and frequency of application of croton oil were increased, and the unrelated promoter anthralin was substituted for croton oil, failed to produce any evidence that differences in promoter degradation contributed to the differences in susceptibility between strains.
实验室小鼠品系对以7,12-二甲基苯并[a]蒽（DMBA）为引发致癌物、巴豆油为促癌剂的两阶段皮肤致癌作用的易感性差异显著。进行本研究是为了阐明品系差异的基础。选用LACA小鼠作为易感品系，BALB/c小鼠作为抗性品系。在LACA小鼠中，DMBA作为完全致癌物比在BALB/c小鼠中更有效。然而，在两阶段致癌过程中对这两个品系进行的DMBA剂量反应研究表明，DMBA代谢活化成活性致癌物在抗性品系中并非限制因素。在一阶段和两阶段致癌过程中观察到的对DMBA反应的品系差异可能反映了DMBA在这两个品系中也作为促癌剂的能力。然而，品系在修复受损DNA能力上存在差异的可能性并未被排除。与DMBA等多环芳烃致癌物不同，佛波酯促癌剂（巴豆油中的活性成分）似乎不需要代谢活化。然而，它们会被表皮细胞和其他细胞降解并失活。增加巴豆油的应用剂量和频率以及用无关促癌剂蒽林替代巴豆油的实验，均未提供任何证据表明促癌剂降解差异导致了品系间易感性差异。
