Two 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 prove to be a particularly sensitive genetic marker of malignancy. The aim of this study was to relate our current knowledge of polychlorinated biphenyl (PCB) bioactivation and polycyclic aromatic hydrocarbon (PAH)-induced DNA damage to ras gene activation in liver tumors from dragonets exposed to these environmental carcinogens. We identified a member of the ras gene family in the marine fish dragonet (Callionymus lyra). 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 level and perfect homology at the amino-acid level. In a pilot study, we collected dragonets from the Seine estuary, an area highly contaminated with PAHs and PCBs. An increase in DNA adducts and an accumulation of ortho- and non-ortho-substituted chlorobiphenyls (CB-77, CB-126, and CB-169) were observed in the livers, a finding that correlates well with the levels of PAHs and PCBs in the sediment. Although liver neoplasia was uncommon, a codon 11 mutation was found in two fish with liver cell hyperplasia, suggesting a possible correlation between hepatic precancerous lesions and ras gene activation in dragonets.
Vincent
F
F
Laboratoire d'Ecotoxicologie-IFREMER, Nantes, France.
de Boer
J
J
Pfohl-Leszkowicz
A
A
Cherrel
Y
Y
Galgani
F
F
D000818:Animals; D001483:Base Sequence; D002273:Carcinogens; D003001:Cloning, Molecular; D018736:DNA Adducts; D004781:Environmental Exposure; D005399:Fishes / Q000235:genetics*; D005602:France; D011905:Genes, ras; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011078:Polychlorinated Biphenyls; D011084:Polycyclic Aromatic Hydrocarbons; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D002273:Carcinogens; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D011078:Polychlorinated Biphenyls