Biomarkers of individual susceptibility to carcinogens: application for biological monitoring.
In order to develop new markers of individual susceptibility to various human carcinogens, we studied some parameters of formation and metabolism of carcinogens, as well as DNA adducts formation and DNA repair in animals and humans. Following an i.p. administration of benzo(a)pyrene (BP) to the rats, levels of urinary excretion of BP-7,8-diol correlated with tumour latency. A high correlation was found between excretion of this metabolite and BP-DNA adducts level in the liver. Healthy smokers excreted higher quantities of BP-7,8-diol, than smoking lung cancer patients, thus confirming the suggestion on existence of cancer-prone phenotype. N-nitroso compounds formed most efficiently in stomach juice of children with superficial gastritis who therefore could be at high risk of stomach cancer. N-ethyl-N'-nitro-N-nitrosoguanidine induced stomach cancer earlier in monkeys with a low level of DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGT) in gastric mucosa. Overall, these markers can be helpful in predicting individual susceptibility to carcinogens.
Likhachev
A J
AJ
N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia.
Beniashvili
D Sh
DSh
Bykov
V J
VJ
Kazanova
O I
OI
Loktionova
N A
NA
Tyndyk
M L
ML
Yatsuk
O S
OS
Yermilov
V B
VB
Zabezhinski
M A
MA
D000328:Adult; D000367:Age Factors; D000818:Animals; D001564:Benzo(a)pyrene / Q000009:adverse effects / Q000378:metabolism*; D001580:Benzopyrenes / Q000032:analysis; D015415:Biomarkers / Q000032:analysis*; D002273:Carcinogens / Q000032:analysis*; D002648:Child; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D004101:Dihydroxydihydrobenzopyrenes / Q000032:analysis; D004198:Disease Susceptibility; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000201:enzymology; D005756:Gastritis / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology; D008252:Macaca fascicularis; D008297:Male; D008780:Methyltransferases / Q000378:metabolism; D008875:Middle Aged; D009603:Nitroso Compounds / Q000009:adverse effects / Q000378:metabolism*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D051381:Rats; D012907:Smoking / Q000378:metabolism; D013274:Stomach Neoplasms / Q000209:etiology
D001580:Benzopyrenes; D015415:Biomarkers; D002273:Carcinogens; D004101:Dihydroxydihydrobenzopyrenes; D009603:Nitroso Compounds; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; C021338:3-hydroxybenzo(a)pyrene; D004247:DNA; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase