Influence of isopropylvaleramide and allylisopropylacetamide on transformation of C3H/10T1/2 cells induced by benzo[a]pyrene derivatives.

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.