Autrup H, Harris C C, Fugaro S, Selkirk J K
Chem Biol Interact. 1977 Sep;18(3):337-47. doi: 10.1016/0009-2797(77)90019-9.
The effect of various co- and anti-carcinogens of colon carcinogenesis on the metabolism of benzo(a)pyrene (BP) in cultured rat colon is reported. Rat colon enzymatically converted BP into metabolites which bind to cellular macromolecules i.e., DNA and protein. Activity of aryl hydrocarbon hydroxylase (AHH) activity and binding levels of BP to macromolecules were higher in the descending colon when compared to other segments. The major metabolites of BP, extractable with ethylacetate, were quinones, tetrols, 7,8-diol and a peak containing 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene and 7,8,9-trihydroxy-7,8-dihydrobenzo(a)pyrene. The binding levels of BP to DNA and protein in the explant was lowered by co-incubation with 7,8-benzoflavone (7,8-BF) (3.6 and 18.0 micron), a known inhibitor of AHH, and with disulfiram (100 micron), an anti-oxidant. The absence of vitamin A in the media also resulted in a lower level of BP binding to DNA and protein and in lower activity of AHH. Pretreatment with known inducers of AHH such as phenobarbital (PB) or benz(a)anthracene (BA), did not have any significant effect on the binding levels of BP to DNA or on the AHH activity. Of the bile acids investigated only taurodeoxycholic acid significantly increased the binding level of BP to DNA.
报道了结肠致癌作用的各种协同致癌物和抗癌物对培养的大鼠结肠中苯并(a)芘（BP）代谢的影响。大鼠结肠可将BP酶促转化为与细胞大分子即DNA和蛋白质结合的代谢产物。与其他节段相比，降结肠中的芳烃羟化酶（AHH）活性以及BP与大分子的结合水平更高。可用乙酸乙酯萃取的BP主要代谢产物为醌、四醇、7,8 -二醇以及一个包含9,10 -二羟基 - 9,10 -二氢苯并(a)芘和7,8,9 -三羟基 - 7,8 -二氢苯并(a)芘的峰。通过与已知的AHH抑制剂7,8 -苯并黄酮（7,8 - BF）（3.6和18.0微米）以及抗氧化剂双硫仑（100微米）共同孵育，外植体中BP与DNA和蛋白质的结合水平降低。培养基中缺乏维生素A也导致BP与DNA和蛋白质的结合水平降低以及AHH活性降低。用已知的AHH诱导剂如苯巴比妥（PB）或苯并(a)蒽（BA）预处理，对BP与DNA的结合水平或AHH活性没有任何显著影响。在所研究的胆汁酸中，只有牛磺脱氧胆酸显著增加了BP与DNA的结合水平。
