Role of the Bay- and L-Regions in the Metabolic Activation and Carcinogenicity of Picene and Dibenz[ a,h ]anthracene

Abstract

Early carcinogenicity tests found no evidence of activity for picene but found considerable initiating and carcinogenic activity for DBA. More recent investigation suggests that both pentacyclics are complete carcinogens when administered as single s.c. injections in NMRI mice, despite findings that picene acts as neither an initiating nor promoting agent. To investigate this contradiction, the complete carcinogenicity of both isomers was compared by s.c. injection in female Sprague-Dawley rats. The results demonstrated that 1 µmol of DBA administered three times weekly for 20 doses, induced sarcomas in all test animals by 33 weeks (100%). Similar treatment with picene did not induce sarcoma in any test animals by 37 weeks (0%). These present results agree with the earlier studies. It follows then that the metabolic activation and carcinogenicity of DBA and picene are dependent on the presence of an L-region, but are independent of the presence of a bay-region.

Theoretical studies on the carcinogenicity of polycyclic aromatic hydrocarbons

“…It is the farthest from the ring and, therefore, the initial interactions with the electrophiles may be occurring at these places. The reactivity of such isolated regions is well known,3, 65 and the high reactivity of the 9 and 10 carbon atoms of anthracene (L regions) can be considered as an example. In short, all the regions in the molecule are important and they may have significant roles to play in the carcinogenic process, as the V min analysis is not giving any clear preference of one region over the other for the observed carcinogenicity.…”

“…Even though these molecules possess a homogeneous structure, their carcinogenic activity (CA) varies widely from highly active to inactive. Immense studies have been contributed to find a relation between the structure of carcinogenic PAHs and their carcinogenic potencies 2–20. The first investigation goes back to 1930s with the pioneer work of Cook et al,21, 22 who tried to correlate the CA with some geometrical features of the molecule.…”