LacI transgenic animal study: relationships among DNA-adduct levels, mutant frequencies and cancer incidences.
In the processes of carcinogenesis caused by genotoxic carcinogens, DNA-adduct formation and resultant genetic changes are crucially important. In this report, the relationship between DNA-adduct levels and mutant frequencies (MFs), DNA-adduct levels and cancer incidences, and MFs and cancer incidences induced by heterocyclic amines (HCAs), to which humans are exposed on daily basis were investigated. There was no direct correlation between adduct levels and MFs detected after feeding Big Blue mice with 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), in a comparison among various organs. Further, there was no direct correlation between DNA-adduct levels and cancer incidences, in a comparison among various organs of F344 rats. Since DNA-adducts are fixed as mutations after cell proliferation, and mutations in cancer-related genes result in cancer development, it is expected that MFs directly correlate with cancer incidences. However, there was no direct correlation between MFs and cancer incidences. Possible mechanisms involved in the discordance between DNA damage markers and cancer incidences are discussed.
Nagao
M
M
Biochemistry Division, National Cancer Center Research Institute, Tsukiji 5, Chuo-ku, 104-0045, Tokyo, Japan. mnago@nodai.ac.jp
Ochiai
M
M
Okochi
E
E
Ushijima
T
T
Sugimura
T
T
D000588:Amines / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D001426:Bacterial Proteins / Q000235:genetics*; D002273:Carcinogens / Q000633:toxicity; D018736:DNA Adducts; D029968:Escherichia coli Proteins; D005260:Female; D006571:Heterocyclic Compounds / Q000633:toxicity*; D006801:Humans; D056968:Lac Repressors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D011804:Quinolines / Q000633:toxicity; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*
D000588:Amines; D001426:Bacterial Proteins; D002273:Carcinogens; D018736:DNA Adducts; D029968:Escherichia coli Proteins; D006571:Heterocyclic Compounds; D056968:Lac Repressors; D011804:Quinolines; D012097:Repressor Proteins; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline