Tumor promoter induces sister chromatid exchanges: relevance to mechanisms of carcinogenesis.
Tumor promoter induces sister chromatid exchanges: relevance to mechanisms of carcinogenesis.
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肿瘤启动子诱导姐妹染色单体交换：与致癌机制的相关性。
DOI：
10.1073/pnas.75.12.6149
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发表时间：
1978
影响因子：
11.1
通讯作者：
M. Radman
中科院分区：
文献类型：
--
作者：
A. Kinsella;M. Radman
12-O-十四烷酰基佛波醇13-乙酸酯（TPA）是一种强有力的肿瘤促进剂，可诱导姐妹染色单体交换（SCE），而非促进衍生物4-O-甲基-TPA则不能。肿瘤促进抑制剂--抗痛剂、亮抑酶肽和氟轻松--抑制TPA诱导的SCE的形成。TPA是一种在不存在DNA损伤、染色体畸变、诱变或显著毒性的情况下诱导SCE的独特试剂。因为TPA已知诱导几种基因功能，我们推测它也可能诱导参与遗传重组的酶。因此，肿瘤促进中的不可逆步骤可能是异常有丝分裂分离事件导致致癌物/诱变剂诱导的隐性遗传或表观遗传染色体变化表达的结果。
12-O-Tetradecanoylphorbol 13-acetate (TPA), a powerful tumor promoter, is shown to induce sister chromatid exchanges (SCEs), whereas the nonpromoting derivative 4-O-methyl-TPA does not. Inhibitors of tumor promotion--antipain, leupeptin, and fluocinolone acetonide--inhibit formation of such TPA-induced SCEs. TPA is a unique agent in its induction of SCEs in the absence of DNA damage, chromosome aberrations, mutagenesis, or significant toxicity. Because TPA is known to induce several gene functions, we speculate that it might also induce enzymes involved in genetic recombination. Thus, the irreversible step in tumor promotion might be the result of an aberrant mitotic segregation event leading to the expression of carcinogen/mutagen-induced recessive genetic or epigenetic chromosomal changes.