Hamilton S M, Teel R W
Department of Physiology and Pharmacology School of Medicine, Loma Linda University, CA 92350.
Anticancer Res. 1994 May-Jun;14(3A):1089-94.
Benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) strongly inhibited the N-pyridine oxidation and alpha-carbon hydroxylation pathways of the in vitro metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by Syrian golden hamster liver microsomes from saline-injected (noninduced) animals. PEITC was more potent than BITC. NNK-reduction was enhanced by both isothiocyanates. Both N-oxidation and alpha-hydroxylation activities were several-fold greater in hamster liver microsomes compared with F344 rat liver microsomes. Consequently, the inhibitory effect of BITC and PEITC on rat liver microsomes (noninduced) was not as pronounced. NNK-reduction in rat liver microsomes was not significantly different from hamster and was not enhanced by BITC and PEITC. Neither BITC nor PEITC had a strong inhibitory effect on the in vitro metabolism of benzo[a]pyrene (BaP) by either hamster or F344 rat liver microsomes from beta-naphthoflavone treated animals. The extent of BaP metabolism was similar for the two microsome groups. Since the metabolism of NNK and BaP depends upon cytochrome P450-mediated reactions that may utilize different isozymes of cytochrome P450, our data suggest that BITC and PEITC may inhibit the activity of some isozymes and not others. Our results also indicate that the inhibition of the metabolism of NNK by isothiocyanates as previously described for the mouse and rat can now be extended to include the hamster as well.
苄基异硫氰酸酯（BITC）和苯乙基异硫氰酸酯（PEITC）强烈抑制了来自注射生理盐水（未诱导）动物的叙利亚金仓鼠肝微粒体对烟草特异性亚硝胺4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）的体外代谢中的N-吡啶氧化和α-碳羟基化途径。PEITC比BITC更有效。两种异硫氰酸酯均增强了NNK的还原作用。与F344大鼠肝微粒体相比，仓鼠肝微粒体中的N-氧化和α-羟基化活性高出几倍。因此，BITC和PEITC对大鼠肝微粒体（未诱导）的抑制作用不那么明显。大鼠肝微粒体中的NNK还原与仓鼠没有显著差异，并且未被BITC和PEITC增强。BITC和PEITC对来自β-萘黄酮处理动物的仓鼠或F344大鼠肝微粒体对苯并[a]芘（BaP）的体外代谢均没有强烈的抑制作用。两个微粒体组的BaP代谢程度相似。由于NNK和BaP的代谢取决于细胞色素P450介导的反应，这些反应可能利用细胞色素P450的不同同工酶，我们的数据表明BITC和PEITC可能抑制某些同工酶的活性而不抑制其他同工酶。我们的结果还表明，如先前在小鼠和大鼠中所描述的，异硫氰酸酯对NNK代谢的抑制作用现在也可以扩展到仓鼠。
