Kinsella A R, Radman M
Proc Natl Acad Sci U S A. 1978 Dec;75(12):6149-53. doi: 10.1073/pnas.75.12.6149.
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.
12 - 十四酰佛波醇 - 13 - 乙酸酯（TPA）是一种强效肿瘤促进剂，已证明它能诱导姐妹染色单体交换（SCEs），而非促进性衍生物4 - O - 甲基 - TPA则不能。肿瘤促进抑制剂——抑肽酶、亮抑酶肽和醋酸氟轻松——可抑制此类TPA诱导的SCEs的形成。TPA在不造成DNA损伤、染色体畸变、诱变或显著毒性的情况下诱导SCEs，是一种独特的物质。由于已知TPA能诱导多种基因功能，我们推测它可能还会诱导参与基因重组的酶。因此，肿瘤促进过程中的不可逆步骤可能是异常有丝分裂分离事件的结果，该事件导致致癌物/诱变剂诱导的隐性遗传或表观遗传染色体变化的表达。
