DISTRIBUTION AND BINDING OF [C-14] ACRYLAMIDE TO MACROMOLECULES IN SENCAR AND BALB/C MICE FOLLOWING ORAL AND TOPICAL ADMINISTRATION

To determine if differences in acrylamide distribution or its binding to DNA could be responsible for the reported higher incidence of skin papillomas observed after oral administration compared to topical application, [14C]acrylamide was administered by topical application and oral intubation to male SENCAR and BALB/mice. Portions of lung, liver, stomach, testes and skin were removed, and 14C was measured at 15 min, 30 min, 1, 6, 12, 24 and 48 h. Binding to DNA, RNA and protein was measured at 6 and 48 h. Following oral administration, few strain differences in distribution or binding were noted. After topical application, SENCAR mice generally showed higher tissue concentrations at the early time periods but not at the later ones. Comparing the 2 routes, comparable concentrations were observed in all tissues except the skin where the amount of [14C]acrylamide after topical application was .apprx. 100-fold that observed after oral administration. The effect of route on papilloma formation was not explained on the basis of a difference in distribution or binding to DNA in the target organ. The binding of acrylamide to DNA in skin was similar in SENCAR and BALB/c mice indicating that the greater susceptibility of the SENCAR mice to tumorigenesis was not explained simply on the basis of distribution or macromolecular binding.