Species-specific differences in hepatic mutant frequency and mutational spectrum among lambda/lacI transgenic rats and mice following exposure to aflatoxin B1.

Abstract

In vivo mutations were studied in lambda/lacI (Big Blue) transgenic C57BL/6 mice and F344 rats following exposure to either AFB1 (aflatoxin B1) or DMSO vehicle. Fourteen days after exposure, livers were removed for DNA extraction and subsequent mutational analysis of the lacI gene. Mice injected with a single i.p. dose of AFB1 at 2.5 mg/kg did not show a significant increase in liver mutant frequency relative to vehicle-treated controls. DNA sequence analysis of lacI mutations collected from the AFB1-treated mice showed a pattern of mutation similar to that of the previously observed spontaneous mouse liver mutational spectrum. In contrast, rats subjected to one-tenth the mouse AFB1 dosage responded with an approximate 20-fold induction in liver mutant frequency over background. Sequencing of lacI mutations also revealed spectral differences between vehicle- and AFB1-treated rats. A large increase in G:C-->T:A transversions was observed among lacI mutations isolated from the AFB1-treated rats. This work is among the first multi-species in vivo mutagenicity studies using transgenic rodents harboring the same shuttle vector. Such multi-species in vivo assays may prove to be valuable in the areas of mechanistic analysis and risk assessment.