Two cases ofras mutation associated with liver hyperplasia in dragonets (Callionymus lyra) exposed to polychlorinated biphenyls and polycyclic aromatic hydrocarbons

Although the effects of polychlorinated biphenyls (PCBs) on human lung carcinogenesis are suggested from the massive PCBs poisoning that occurred in Japan designated "Yusho," the detailed molecular mechanism are unknown. 1 nitropyrene (1-NP), an ubiquitous and abundant environmental pollutant, is known to be detected in lung tissues derived from patients with lung cancer in Japan, and its relation to lung carcinogenesis is also suggested. We investigated the effects of PCBs (Kanechlor-400) on 1-NP-induced lung tumorigenesis in A/J mice. PCBs were administered intraperitoneally followed by ip injection of 1-NP. The lung lesions were examined 18 weeks after the final treatment. In the control group, no neoplastic lesions were induced in the lung. In the PCB group, preneoplastic lesions such as hyperplasia and adenoma were induced in 2/10 (20%) mice. In 1-NP group and in PCB + 1-NP group, lung lesions including adenocarcinoma were induced in 16/20 (80%) and 13/13 (100%) mice, respectively. Both the number and the size of tumors in PCB + 1-NP group were significantly greater than those in 1-NP group. K-ras gene mutation, CAA to CGA in codon 61 or GGT to GAT in codon 12, was found in either 1-NP group or PCB + 1-NP group but not in the PCB group. There was no difference in the pattern of K-ras mutation associated with the pretreatment with PCBs. These results suggest that PCBs promote 1-NP-induced lung tumorigenesis and may support, at least in part, the mechanism of the high incidence of lung cancer in patients with Yusho.

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Genotoxic Impact of ‘Erika’ Petroleum Fuel on Liver of the Fish Solea Solea

Amat¹,

Burgeot²,

Castegnaro³

et al.

Environmental Chemistry

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On 12 December 1999, one third of the load of the tanker 'Erika' , amounting to about 10 000 t crude oil flowed into sea waters close to the French Atlantic Coast (Finistère region). The spilled oil was fuel No. 6, a heavy or residual fuel that is a complex mixture of polycyclic aromatic compounds (PAC) of high molecular weight. Some polycyclic aromatic compounds are genotzoxic substances that induce carcinogenic lesions in laboratory animals. DNA adducts, reflecting genotoxic effects, are used as biomarker of early pollution. In this study, the genotoxic impact of the 'Erika' oil was assessed by studying the presence of DNA adduct in the liver of immature fishes (Solea solea) from four locations of the French Brittany coasts, two, six and nine months after the disaster. Two months after the spill, a high amount of DNA adducts was found in samples from all locations (92 to 290 DNA adduct/10 9 nucleotides). DNA adducts were more persistent in the North than in the South of the affected French Brittany coasts. In September, no significant difference was observed between the locations. When incubated in presence of an 'Erika' fuel extract, DNA adduct patterns similar to those obtained from the liver of Solea solea liver are observed both, in cell culture (HePG2) and, in presence of fish liver microsomes.

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Two cases ofras mutation associated with liver hyperplasia in dragonets (Callionymus lyra) exposed to polychlorinated biphenyls and polycyclic aromatic hydrocarbons

Cited by 22 publications

References 25 publications

Nmethyl-N-nitrosourea (MNU) induces papillary thyroid tumours which lackras gene mutations in the hermaphroditic fishRivulus marmoratus

Nmethyl-N-nitrosourea (MNU) induces papillary thyroid tumours which lackras gene mutations in the hermaphroditic fishRivulus marmoratus

Polychlorinated biphenyls promote 1‐nitropyrene‐induced lung tumorigenesis without the induction of K‐ras gene mutation in A/J mice

Genotoxic Impact of ‘Erika’ Petroleum Fuel on Liver of the Fish Solea Solea

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