Krolewski B, Little J B
Carcinogenesis. 1985 Jan;6(1):7-11. doi: 10.1093/carcin/6.1.7.
We examined the effect of aliphatic amides isopropylvaleramide (IVA) and allylisopropylacetamide (AIA) on the oncogenic transformation of C3H/10T1/2 cells induced by benzo[a]pyrene (B[a]P) or its proximate and ultimate metabolites (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (B[a]P-7,8-diol) and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (B[a]P-diol-epoxide), respectively. IVA and AIA given prior to, simultaneously with, or for 24 h intervals beginning up to 48 h after removal of carcinogens significantly suppressed transformation induced by B[a]P or the 7,8-diol metabolite. Both modifiers were most effective when added for 24 h immediately following carcinogen exposure. IVA and AIA were also very potent inhibitors of B[a]P-diol-epoxide transformation; however they were most effective when added for 24 h simultaneously with the B[a]P-diol-epoxide. No significant difference in B[a]P-diol-epoxide binding to DNA in C3H/10T1/2 cells was observed during 1 or 24 h exposure to this carcinogen in the presence or absence of IVA or AIA. Neither modifier affected X-ray transformation when added for 24 h immediately following X-irradiation of C3H/10T1/2 cells. These results suggest that AIA and especially IVA might be important tools in studies directed at non-metabolic aspects of B[a]P carcinogenesis.
我们研究了脂肪族酰胺异丙基戊酰胺（IVA）和烯丙基异丙基乙酰胺（AIA）对苯并[a]芘（B[a]P）或其近端及最终代谢产物（±）-反式-7,8-二羟基-7,8-二氢苯并[a]芘（B[a]P-7,8-二醇）和（±）-7β,8α-二羟基-9α,10α-环氧-7,8,9,10-四氢苯并[a]芘（B[a]P-二醇环氧化物）诱导的C3H/10T1/2细胞致癌转化的影响。在去除致癌物之前、同时或在去除致癌物后长达48小时开始以24小时间隔给予IVA和AIA，可显著抑制B[a]P或7,8-二醇代谢产物诱导的转化。两种调节剂在致癌物暴露后立即添加24小时时最为有效。IVA和AIA也是B[a]P-二醇环氧化物转化的强效抑制剂；然而，它们在与B[a]P-二醇环氧化物同时添加24小时时最为有效。在存在或不存在IVA或AIA的情况下，C3H/10T1/2细胞在暴露于该致癌物1小时或24小时期间，未观察到B[a]P-二醇环氧化物与DNA结合有显著差异。在对C3H/10T1/2细胞进行X射线照射后立即添加24小时，两种调节剂均未影响X射线诱导的转化。这些结果表明，AIA尤其是IVA可能是针对B[a]P致癌作用非代谢方面研究的重要工具。
