Otsuka C, Miura K F, Ishidate M
Chromosome Research Center (CRC), Olympus Optical Co., Ltd., Tokyo, Japan.
Mutat Res. 1996 Nov 4;371(1-2):23-8. doi: 10.1016/s0165-1218(96)90091-9.
When metabolically activated, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine isolated from cooked food, is clastogenic in cultured Chinese hamster and human cells. Secondary metabolites of PhIP are formed via acetyltransferase (AT) and sulfotransferase (ST) activity; however, which is responsible for its clastogenic effect is unknown. We addressed this question. We used a parental Chinese hamster lung cell line and three sublines transfected with different AT genes to test the clastogenic (i.e., micronucleus-inducing) effects of metabolically activated PhIP and 7,12-dimethylbenz[a]anthracene (DMBA) in the presence and absence of pentachlorophenol (PCP), a ST inhibitor. PhIP was significantly more clastogenic in the three AT-enriched sublines than in the parental line (p < 0.001). DMBA (a ST-activated mutagen), on the other hand, equally induced MNs in all the cell lines. When PCP was added to the test system, the MN-induction ability of DMBA, but not of PhIP, decreased significantly (p < 0.001). These findings strongly suggest that PhIP clastogenicity is due to AT activity and not to ST activity.
2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）是一种从熟食中分离出的杂环胺，在代谢激活后，对中国仓鼠和人类培养细胞具有致染色体断裂作用。PhIP的次级代谢产物是通过乙酰转移酶（AT）和磺基转移酶（ST）的活性形成的；然而，尚不清楚是哪种酶导致了其致染色体断裂作用。我们研究了这个问题。我们使用了一个亲代中国仓鼠肺细胞系和三个转染了不同AT基因的亚系，来测试在存在和不存在五氯苯酚（PCP，一种ST抑制剂）的情况下，代谢激活的PhIP和7,12-二甲基苯并[a]蒽（DMBA）的致染色体断裂（即微核诱导）作用。在三个富含AT的亚系中，PhIP的致染色体断裂作用明显强于亲代细胞系（p < 0.001）。另一方面，DMBA（一种由ST激活的诱变剂）在所有细胞系中诱导微核的能力相同。当向测试系统中加入PCP时，DMBA的微核诱导能力显著下降（p < 0.001），而PhIP的微核诱导能力没有下降。这些发现有力地表明，PhIP的致染色体断裂作用是由于AT的活性，而不是ST的活性。
