K-ras oncogene DNA sequences in pink salmon in streams impacted by the Exxon Valdez oil spill: No evidence of oil-induced heritable mutations

LGL Alaska Research Associates, Anchorage 99518, USA.
Ecotoxicology (Impact Factor: 2.71). 09/2002; 11(4):233-41. DOI: 10.1023/A:1016391919495
Source: PubMed

ABSTRACT It was hypothesized in previous studies that the Exxon Valdez oil spill in Prince William Sound, Alaska, induced heritable mutations and resulted in mortality of pink salmon (Oncorhynchus gorbuscha) embryos. In one of these studies, laboratory exposure of pink salmon embryos to crude oil resulted in apparent mutation-induction in exon 1 and exon 2 of the K-ras oncogene, but no fish from the area impacted by the oil spill were analyzed. We assessed K-ras exon 1 and exon 2 DNA sequences in pink salmon from five streams that were oiled and five streams that were not oiled by the Exxon Valdez oil spill in Prince William Sound, and two streams with natural oil seeps and one stream without seeps on the Alaska Peninsula. Of the 79 fish analyzed for exon 1 and the 89 fish analyzed for exon 2, none had the nucleotide substitutions representing the mutations induced in the laboratory study. Other variable nucleotides occurred in similar proportions in oiled and non-oiled streams and probably represent natural allelic variation. These data do not support the hypothesis that heritable mutations in the K-ras gene were induced by the Exxon Valdez oil spill or oil seeps.

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Available from: Matthew A Cronin, Sep 25, 2015
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    • "When spilt, for instance due to shipwrecking, these products can induce modifications in the marine environment causing disruption at the ecosystem level. For example, in situ contact with field and high concentrations of PAHs could induce external abnormalities (Pollino and Holdway, 2002), somatic mutations (Cronin et al., 2002; Roy et al., 1999) and immunodepression (Holladay et al., 1998) in fish. Many studies have therefore focused on the immune systems of fish whose some compounds are often used as biomarkers of xenobiotic effects. "
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    Toxicology in Vitro 03/2009; 23(2):235-41. DOI:10.1016/j.tiv.2008.12.001 · 2.90 Impact Factor
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    • "Regarding direct and/or indirect involvement of EDCs in carcinogenesis , there were some examples in Winter flounder (Pleuronectes americanus) exposed to polycyclic aromatic hydrocarbons (PAHs) (Wirgin et al., 1989), tomcod (Microgadus tomcod) exposed to polychlorinated biphenyls (PCBs) (McMahon et al., 1990), and dragonets (Callionymus lyra) exposed to PAH and PCB (Vincent et al., 1998). However, Cronin et al. (2002) found that the heavy oil-derived EDC could not induce heritable mutations in Ki-ras as shown for example in the Exxon Valdez oil spill. This suggests that the effect of chemicals on ras genes in fish and its role in carcinogenesis upon EDC exposure still remain uncertain (Lee et al., 2008c). "
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    ABSTRACT: The hermaphroditic fish Krytolebias marmoratus is a potential fish model for study of tumour development. Recently, sequences and expression of some oncogenes and tumor suppressor gene have been studied in K. marmoratus. To get a better understanding of oncogene expression at different development stage, and in different tissues three R-ras genes were cloned and fully sequenced. Expression of these R-ras genes (R-ras1, R-ras2, R-ras3) was also studied in fish exposed to endocrine-disrupting chemicals (EDCs). Liver showed the highest level of expression compared to other tissues, even though each R-ras gene showed different expression patterns in tissues. Interestingly, in secondary male (ovary atresia stage), expression levels of three R-ras genes was lower compared to hermaphrodites. At different developmental stages, R-ras2 gene showed most pronounced expression at early embryogenesis but at stage 5 (hatchling stage) and juvenile stage, R-ras3 gene showed the highest expression. After the juvenile stage, R-ras1 gene was upregulated compared to other R-ras genes, which showed the highest expression at the hermaphroditic stage. When fish were exposed to 17-beta-estradiol (E2), a natural estrogen and tamoxifen, a nonsteroidal estrogen antagonist and three EDCs viz., 4-n-nonylphenol (NP), bisphenol A (BPA), and 4-tert-octylphenol (OP), all the three R-ras genes were induced, except in the fish exposed to tamoxifen. These results suggest that EDCs modulate the expression of R-ras genes and thus affect subsequent signal transduction and tumor development.
    Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 11/2008; 149(3):433-9. DOI:10.1016/j.cbpc.2008.10.102 · 2.30 Impact Factor
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    • "Recently, ras mutation analysis has been performed in pink salmon (Oncorhynchus gorbuscha) embryos (Cronin et al., 2002) to confirm the earlier observation of Roy et al. (1999) who had reported Ki-ras mutations in pink salmon embryos exposed to weathered Prudhoe Bay oil samples. However, study of Cronin et al. (2002) in field samples revealed that heritable mutations in Ki-ras are not induced by Exxon Valdez oil spill or oil seeps. This suggests that effect of chemicals on ras genes in fish still remains uncertain. "
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