Baird W M, Salmon C P, Diamond L
Cancer Res. 1984 Apr;44(4):1445-52.
Benzo(e)pyrene (BeP) is a cocarcinogen with benzo(a)pyrene (BaP) and an anticarcinogen with 7,12-dimethylbenz(a)anthracene (DMBA) in mouse skin initiation-promotion assays (Slaga, T.J., Jecker, L., Bracken, W.M. and Weeks C.E. Cancer Lett. 7: 51-59, 1979). We have investigated the effects of BeP on the metabolic activation of BaP and DMBA in early-passage cultures of Syrian hamster embryo cells. BeP had no effect on BaP-induced mutation frequencies in hamster embryo cell-mediated assays with V79 target cells. However, it inhibited the DMBA-induced mutagenesis by as much as 10-fold at the highest dose tested. Low doses of BeP did not affect the total amount of BaP metabolized, but the proportion of water-soluble metabolites was reduced, and the proportions of trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene and trans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene were increased. Higher doses did decrease BaP metabolism and caused similar alterations in the metabolite profile. In cultures treated with trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, BeP greatly reduced the oxidative metabolism of this diol. BeP inhibited DMBA metabolism at all doses tested; the proportion of water-soluble metabolites formed was decreased, and the proportions of trans-8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene and trans-3,4-dihydro-3,4-dihydroxy-7,12-dimethylbenz(a)anthracene were increased. The results demonstrate that BeP is an effective inhibitor of the secondary oxidation of carcinogenic hydrocarbon diols required to convert diols which are proximate carcinogens to ultimate carcinogens such as diol-epoxides. The balance between (a) limited inhibition with consequent increase in total exposure to the ultimate carcinogenic form and (b) sufficient inhibition to reduce exposure to the ultimate carcinogenic form may determine whether BeP acts as a co- or anticarcinogen with a particular carcinogenic hydrocarbon.
在小鼠皮肤启动-促进试验中，苯并(e)芘（BeP）与苯并(a)芘（BaP）一样是一种促癌剂，而与7,12-二甲基苯并(a)蒽（DMBA）相反是一种抗癌剂（斯拉加，T.J.，杰克尔，L.，布拉肯，W.M.和威克斯，C.E.《癌症通讯》7: 51 - 59，1979）。我们研究了BeP对叙利亚仓鼠胚胎细胞早期传代培养物中BaP和DMBA代谢活化的影响。在以V79靶细胞进行的仓鼠胚胎细胞介导试验中，BeP对BaP诱导的突变频率没有影响。然而，在测试的最高剂量下，它对DMBA诱导的诱变作用的抑制高达10倍。低剂量的BeP不影响BaP代谢的总量，但水溶性代谢物的比例降低，反式-7,8-二氢-7,8-二羟基苯并(a)芘和顺式-9,10-二氢-9,10-二羟基苯并(a)芘的比例增加。较高剂量确实会降低BaP的代谢，并导致代谢物谱发生类似变化。在用反式-7,8-二氢-7,8-二羟基苯并(a)芘处理的培养物中，BeP大大降低了这种二醇的氧化代谢。BeP在所有测试剂量下均抑制DMBA的代谢；形成的水溶性代谢物的比例降低，反式-8,9-二氢-8,9-二羟基-7,12-二甲基苯并(a)蒽和顺式-3,4-二氢-3,4-二羟基-7,12-二甲基苯并(a)蒽的比例增加。结果表明，BeP是致癌烃二醇二级氧化的有效抑制剂，这种氧化是将作为近致癌物的二醇转化为诸如二醇环氧化物等最终致癌物所必需的。（a）有限抑制导致最终致癌形式的总暴露增加与（b）足够抑制以减少对最终致癌形式的暴露之间的平衡，可能决定了BeP与特定致癌烃一起是作为促癌剂还是抗癌剂。
