Perfluorooctanesulfonate (PFOS) has been widely detected in the environment, wildlife and humans, but few studies have ever examined its mutagenic effect in vivo. In the present study, we use a transgenic fish model, the lambda transgenic medaka, to evaluate the potential mutagenicity of PFOS in vivo following a subchronic exposure of 30 days. The mutant frequency of cII target gene was 3.46 x 10(-5) in liver tissue from control fish, which increased by 1.4-fold to 4.86 x 10(-5) in fish exposed to 6.7 mu g/L PFOS, 1.55-fold to 5.36 x 10(-5) in fish exposed to 27.6 mu g/L PFOS, and 2.02-fold to 6.99 x 10(-5) in fish exposed to 87.6 mu g/L PFOS. This dose-dependent increase of mutant frequency was also accompanied with mutational spectrum changes associated with PFOS exposure. In particular, PFOS-induced mutation was characterized by + 1 frameshift mutations, which increased from 0% in control fish to 13.2% in fish exposed to 27.6 mu g/L PFOS and 14.6% in fish exposed to 87.6 mu g/L PFOS. Our findings provide the first evidence of PFOS's mutagenicity in an aquatic model system. Given the fact that most conventional mutagenic assays were negative for PFOS, we propose that PFOS-induced mutation in liver tissue of. transgenic medaka may be mediated through compromised liver function.
