The Effect of Dietary Restriction on PhIP-Induced Mutation in the Distal Colon and B[a]P- and ENU-Induced Mutation in the Liver of the Rat

Abstract

Abstract: A reduction in dietary intake has been shown to significantly increase the lifespan of rodents, lower the incidence of tumors, and reduce DNA damage. The objective of this study was to determine whether dietary restriction (DR) reduced the frequency of mutation induced by two environmentally relevant metabolically activated mutagens and one direct-acting mutagen in the lacI transgene of male and female Big Blue® rats. Both male and female rats were maintained on either an ad libitum (AL) or a 40%-reduced diet for 22 wk. The mutagenicity of a 100-mg/kg intraperitoneal injection with 2-amino-1-methyl-6-pheny-imidazo[4,5-b] pyridine (PhIP), benzo[a]pyrene (B[a]P), and N-ethyl-N- nitrosourea (ENU) was determined in the colon or liver. The results indicated that DR did not significantly alter the PhIP-induced mutant frequency in male or female colons. DR completely prevented mutagenicity induced by B[a]P in the female liver (2.6 ± 0.6 × 10^-5 vs 10.9 ± 5.8 × 10^-5 in AL females), yet increased the induced frequency in male livers (16.3 ± 3.7 × 10^-5 vs 10.6 ± 1.5 × 10^-5 in AL male livers). Although there was no difference in mutation frequency in the liver between AL and DR females treated with ENU, there was approximately a 40% decrease in induced frequency in DR males compared with AL males. These results indicate that a reduction in dietary intake has no preventive effect against PhIP-induced mutation in the colon, but has sex-dependent protective effects against B[a]P- and ENU-induced mutation in the liver.