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Polycyclic aromatic hydrocarbons: correlations between DNA adducts and ras oncogene mutations
1Biochemistry and Pathobiology Branch (MD-68), National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Mutation Research
|March 5, 1999
Summary
Polycyclic aromatic hydrocarbons (PAHs) can cause cancer by forming DNA adducts that mutate the ras oncogene. The type of DNA adduct formed correlates with specific ras mutations, indicating their role in tumor development.
Area of Science:
- Environmental toxicology
- Molecular carcinogenesis
- Genetics
Background:
- Polycyclic aromatic hydrocarbons (PAHs) are environmental mutagens linked to cancer.
- The formation of DNA adducts by PAHs is a key step in their tumorigenic activity.
- Ras oncogene mutations are frequently observed in PAH-induced tumors.
Purpose of the Study:
- To review studies on the tumorigenic activities of non-nitrogenous PAHs.
- To correlate PAH-DNA adduct structures with ras oncogene mutations in induced tumors.
- To elucidate the role of adduct-directed mutations in PAH-induced carcinogenesis.
Main Methods:
- Review of experimental animal model studies on PAH tumorigenesis.
- Analysis of PAH-DNA adduct formation in target tissues.
- Detection and characterization of ras oncogene mutations in tumors.
Main Results:
- PAHs forming adducts at deoxyadenosine predominantly induce mutations at codon 61.
- PAHs forming adducts at deoxyguanosine primarily induce mutations at codons 12 or 13.
- PAHs adducting both bases induce both types of mutations, supporting adduct-directed mutagenesis.
Conclusions:
- The type of PAH-DNA adduct formed directly influences the mutation spectrum in the ras oncogene.
- Adduct-directed mutations in ras are critically involved in the etiology of PAH-induced tumors.
- Ras mutation spectra can serve as biomarkers for identifying specific PAH adducts.