Effect of caloric restriction on the metabolism of 7-bromobenz[a]anthracene and 7-fluorobenz[a]anthracene by male B6C3F1 mouse liver microsomes: Reduction of metabolic activation pathway

Abstract

The effect of caloric restriction (CR) on the in vitro metabolism of 7-bromobenz[a]anthracene (7-Br-BA) and 7-fluorobenz[a]anthracene (7-F-BA) by liver microsomes isolated from 5-and 12-month-old male B6C3F1 mice was studied. Mice were fed ad libitum (AL), or starting at 14 weeks of age, received 60% of the calories consumed by control mice. After microsomal incubation, metabolites were separated by HPLC and their structures identified by comparison of their spectra with known standards. The metabolites formed were: trans-3,4-dihydrodiol, trans-5,6-dihydrodiol, trans-8,9-dihydrodiol and trans-10,11-dihydrodiol, 5,6-epoxide, and 4-, 5-, 6-, 8-, and 9-phenolic derivatives. The formation of the 7-Br-BA trans-3,4-dihydrodiol and 7-F-BA trans-3,4-dihydrodiol, the proximate mutagens of 7-Br-BA and 7-F-BA, respectively, was lower in microsomal incubation mixtures derived from the 5-month-old CR mice as compared to those from the AL. These results suggest that CR can diminish the genotoxicity of polycyclic aromatic hydrocarbons by directly altering metabolic activation.