Molecular approach in cancer epidemiology: early detection of carcinogen-induced mutations in a whole genome (Review).
Chronic exposure of organisms to endo- or exogenous genotoxic products results in the accumulation of mutations in the genome and eventually to the development of cancers. Early detection of these mutations would allow the identification of at risk individuals who present a high load of mutations either because of an occupational or environmental exposure, or because of less efficient DNA repair processes. However, highly specific and sensitive assays are required to allow the detection of point mutations in a whole genome. We review a long-term study on the mutagenesis induced in E.coli by an aromatic amide, the N-2-acetylaminofluorene. A major contribution of this work was to reveal the presence of specific mutation hot spot sequences. Taking advantage of this observation, we designed a specific, sensitive and semi-quantitative in vitro assay allowing the detection of carcinogen induced mutations. This assay has been validated in vivo and demonstrate the sensitivity of the technique in early detection of mutations and its usefullness in molecular epidemiology, early diagnostic and prognosis.
Burnouf
D
D
Groupe d'Epidemiologie Moleculaire du Cancer, UPR 9003, Centre National de la Recherche Scientifique, Institut de Recherche sur les Cancers de l'Appareil Digestif, 1 Place de l'Hopital, 67097 Strasbourg, France.
Miturski
R
R
Nagao
M
M
Nakagama
H
H
Nothisen
M
M
Wagner
J
J
Fuchs
R P
RP
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D002274:Carcinogens, Environmental / Q000494:pharmacology*; D018736:DNA Adducts / Q000737:chemistry; D016368:Frameshift Mutation; D015894:Genome, Human; D006801:Humans; D009369:Neoplasms / Q000235:genetics*
D002274:Carcinogens, Environmental; D018736:DNA Adducts; D015073:2-Acetylaminofluorene