Species-specific differences in hepatic mutant frequency and mutational spectrum among lambda/lacI transgenic rats and mice following exposure to aflatoxin B-1

In vivo mutations were studied in lambda/lacI (Big Blue(R)) transgenic C57BL/6 mice and F344 rats following exposure to either AFB(1) (aflatoxin B-1) or DMSO vehicle. Fourteen days after exposure, livers were removed for DNA extraction and subsequent mutational analysis of the lad gene, Mice injected with a single i.p. dose of AFB(1) at 2.5 mg/kg did not show a significant increase in liver mutant frequency relative to vehicle-treated controls, DNA sequence analysis of lad mutations collected from the AFB(1)-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 AFB(1) dosage responded with an approximate 20-fold induction in liver mutant frequency over background, Sequencing of lad mutations also revealed spectral differences between vehicle- and AFB(1)-treated rats. A large increase in G:C-->T:A transversions was observed among lad mutations isolated from the AFB(1)-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.