Distribution and macromolecular binding of benzo[a]pyrene in sencar and balb/c mice following topical and oral administration

Abstract

When benzo[a]pyrene (BaP) is used as the initiator in initiation-promotion assays, the topical route of administration has been shown to produce a greater epidermal tumor incidence than do other routes of administration, particularly the oral route. In addition, different strains of mice exhibit varying degrees of susceptibility to two-stage epidermal tumorigenesis using BaP. The SENCAR strain is known to be far more sensitive to epidermal tumor formation following BaP initiation than are other strains, such as the BALB/c strain. To investigate the possible contribution of distribution and binding to DNA in such route and strain differences, the distribution and macromolecular binding of [3H]BaP was examined in the skin, liver, lung, and stomach of SENCAR and BALB/c mice following topical or oral administration of BaP at time periods ranging from 0.5 to 48 h. Levels of labeled material in skin were higher, and the binding of BaP to epidermal DNA was greater following topical administration than following oral administration for mice of both strains. The much greater binding of BaP to epidermal DNA following topical administration may account for the much greater epidermal tumor incidence in mice following topical administration of BaP. Following topical administration, BALB/c mice had generally higher levels of labeled material in whole skin than did SENCAR mice, and the binding of BaP to epidermal DNA at 48 h was greater in BALB/c mice than in SENCAR mice following either route of administration. Thus, the known differences between these two strains in susceptibility to epidermal tumor formation when BaP is used as an initiator cannot be explained on the basis of differences in tissue distribution or the amount of binding to epidermal DNA at the time periods examined.