2 CASES OF RAS MUTATION ASSOCIATED WITH LIVER HYPERPLASIA IN DRAGONETS (CALLIONYMUS-LYRA) EXPOSED TO POLYCHLORINATED-BIPHENYLS AND POLYCYCLIC AROMATIC-HYDROCARBONS

ras gene activation in a naturally exposed feral fish population may p rove to be a particularly sensitive genetic marker of malignancy The a im of this study was to relate Our current knowledge of polychlorinate d biphenyl (PCB) bioactivation and polycyclic aromatic hydrocarbon (PA H)-induced DNA damage to ras gene activation in liver tumors from drag onets exposed to these environmental carcinogens. We identified a memb er of the ras gene family in the marine fish dragonet (Callionymus lyr a). The first two exons of this new sequence showed a very high degree of homology with the human ras genes (81-86%) at the nucleic acid lev el and perfect homology at the amino-acid level. In a pilot study, we collected dragonets from the Seine estuary, an area highly contaminate d with PAHs and PCBs. An increase in DNA adducts and an accumulation o f ortho-a nd non-ortho-substituted chlorobiphenyls (CB-77, CB-126, and CB-169) were observed in the livers, a finding that correlates well w ith the levels of PAHs and PCBs in the sediment. Although liver neopla sia was uncommon, a codon 11 mutation was found in two fish with liver cell hyperplasia, suggesting a possible correlation between hepatic p recancerous lesions and ras gene activation in dragonets. (C) 1998 Wil ey-Liss, Inc.