2-STAGE SKIN CARCINOGENESIS IN SENSITIVE AND RESISTANT MOUSE STRAINS
2-STAGE SKIN CARCINOGENESIS IN SENSITIVE AND RESISTANT MOUSE STRAINS
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DOI：
10.1093/carcin/3.1.99
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发表时间：
1982-01-01
期刊：
影响因子：
4.7
通讯作者：
KOTLARSKI, I
中科院分区：
文献类型：
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作者：
ASHMAN, LK;MURRAY, AW;KOTLARSKI, I
不同品系的实验小鼠对以7，12-二甲基苯并[a]蒽（DMBA）为起始致癌物、巴豆油为促进剂的两阶段皮肤致癌作用的敏感性差异显著。研究了应变差异的基础。LACA小鼠作为敏感品系，BALAB/c小鼠作为抗性品系。DMBA对LACA小鼠的完全致癌作用强于BALB/c小鼠。剂量反应研究表明，DMBA的代谢活化的活性致癌物在2个菌株在2阶段的致癌性表明，在耐药菌株不受限制。DMBA在1、2阶段致癌反应的株系差异可能反映了DMBA在2个株系中作为启动子的能力。菌株修复受损DNA的能力不同的可能性尚未被排除。与DMBA等多环芳烃致癌物不同，佛波醇酯促进剂（巴豆油中的活性成分）似乎不需要代谢活化。它们被表皮细胞和其他细胞降解和灭活。增加巴豆油的施用剂量和频率以及用不相关的启动子蒽林代替巴豆油的实验未能产生任何证据表明启动子降解的差异导致菌株之间的易感性差异。
Strains of laboratory mice vary markedly in their susceptibility to 2-stage skin carcinogenesis using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiating carcinogen and croton oil as promoter. The basis of the strain differences was studied. LACA mice were used as the susceptible strain and BALAB/c mice as the resistant strain. DMBA was a more effective complete carcinogen in LACA mice than in BALB/c mice. Dose-response studies with respect to DMBA in the 2 strains in 2-stage carcinogenesis suggested that metabolic activation of DMBA to the active carcinogen was not limiting in the resistant strain. The strain differences in response to DMBA in 1 and 2 stage carcinogenesis may reflect the ability of DMBA to act as a promoter in the 2 strains. The possibility that the strains vary in their ability to repair damaged DNA has 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. 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.