Aflatoxin B1-induced mitotic recombination in L5178Y mouse lymphoma cells

Aflatoxin B1 is a human hepatocarcinogen, It is also a known point mutagen in bacteria and mammalian cells. This mutagenic activity may be at least pa rtly responsible for its carcinogenic activity. However, recent studies sho w that aflatoxin B1 induces mitotic recombination in the yeast Saccharomyce s cerevisiae, Because numerous reports have implicated mitotic recombinatio n in mechanisms leading to carcinogenesis and because no one has shown that aflatoxin B1 induces recombination in mammalian cells, we decided to exami ne the ability of aflatoxin B1 to induce recombination in a mammalian cell line. We used a combination of methods, analysis for loss of heterozygosity and whole chromosome in situ hybridization, to identify mechanisms of chro mosome mutation, including mitotic recombination in the mammalian L5178Y mo use lymphoma cell system. Our experiments revealed that mitotic recombinati on caused similar to 60% or more of the aflatoxin B1-induced mutagenic lesi ons in this cell system. Thus, mitotic recombination plays an important rol e in aflatoxin B1-induced mutagenesis in mammalian cells and possibly in ch emically induced mutagenesis and carcinogenesis. This work suggests that mu ltiple genetic lesions may be involved in aflatoxin B1-induced pathology.