Dashwood R H, Combes R D, Ashby J
Carcinogenesis. 1986 Jun;7(6):1029-33. doi: 10.1093/carcin/7.6.1029.
6-(p-Dimethylaminophenylazo)benzothiazole (6BT) and 5-(p-dimethylaminophenylazo)indazole (5I) comprise respectively a carcinogen/non-carcinogen pair of monoazo dyes related to the hepatocarcinogen, butter yellow (DAB). While both members of the pair are potent bacterial mutagens in vitro, only 6BT induces unscheduled DNA synthesis in rat liver in vivo. To investigate factors responsible for these divergent activities we have determined in rats: relative rates of uptake from the gut after direct injection of 14C-labelled compound into intestine in situ, and after administration p.o.; distribution in selected tissues and elimination in urine, faeces and bile; binding of both compounds in vivo to liver DNA. The results revealed that, although 5I was taken up from the gut to a lesser extent than 6BT, comparable labelling associated with both compounds was detected in the presumed target organ (the liver). 5I binds in vivo to DNA much less effectively than 6BT. Therefore it would seem that other factors, such as differential metabolism in vivo, are more important than differences in uptake and distribution in accounting for the divergent activities of 6BT and 5I.
6-(对-二甲基氨基苯基偶氮)苯并噻唑(6BT)和5-(对-二甲基氨基苯基偶氮)吲唑(5I)分别构成了一对与肝癌致癌物奶油黄(二甲基氨基偶氮苯,DAB)相关的致癌物/非致癌物单偶氮染料。虽然这两种染料在体外都是强效的细菌诱变剂,但只有6BT能在大鼠肝脏中诱导体内非程序性DNA合成。为了研究导致这些不同活性的因素,我们在大鼠中测定了:将14C标记的化合物原位直接注射到肠道后以及口服给药后从肠道的相对摄取率;在选定组织中的分布以及在尿液、粪便和胆汁中的消除情况;两种化合物在体内与肝脏DNA的结合情况。结果显示,虽然5I从肠道的摄取程度低于6BT,但在假定的靶器官(肝脏)中检测到与两种化合物相关的类似标记。5I在体内与DNA的结合效率远低于6BT。因此,似乎其他因素,如体内的差异代谢,在解释6BT和5I的不同活性方面比摄取和分布的差异更为重要。