Biomarkers for individual susceptibility to carcinogenic agents: excretion and carcinogenic risk of benzo[a]pyrene metabolites.
In rats exposed to a single intraperitoneal dose of 200 mg/kg of the environmental carcinogen benzo[a]pyrene (BP) in sunflower oil, significant individual variations in excretion of the BP activation (BP-7,8-diol) and deactivation (3-OH-BP) derivatives were found. Most rats developed peritoneal sarcomas. Only the levels of BP-7,8-diol excreted in the urine correlated directly with the latency of tumor formation. After a similar exposure to a dose of 100 mg/kg BP, Macaca fascicularis monkeys excreted smaller quantities than rats of both metabolites. After rats were given 10 intraperitoneal injections each of 10 mg/kg of BP in a water-lipid emulsion, the excreted levels of both metabolites after the first, fifth, and tenth injection were lower than those of the rats that received 200 mg/kg. BP metabolites were also detected in the urine of lung cancer patients who were heavy smokers. The applicability of monitoring the excretion of the BP metabolites to predicting individual cancer risk is discussed.
Likhachev
A J
AJ
N. N. Petrov Research Institute of Oncology, St. Petersburg, Russia.
Beniashvili
D Sh
DSh
Bykov
V J
VJ
Dikun
P P
PP
Tyndyk
M L
ML
Savochkina
I V
IV
Yermilov
V B
VB
Zabezhinski
M A
MA
D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001580:Benzopyrenes / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D004198:Disease Susceptibility; D005243:Feces / Q000737:chemistry*; D018219:Histiocytoma, Benign Fibrous / Q000139:chemically induced* / Q000652:urine; D008252:Macaca fascicularis; D008297:Male; D010534:Peritoneal Neoplasms / Q000139:chemically induced* / Q000652:urine; D051381:Rats; D012307:Risk Factors; D013045:Species Specificity
D001580:Benzopyrenes; D014408:Biomarkers, Tumor; D004101:Dihydroxydihydrobenzopyrenes; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; C021338:3-hydroxybenzo(a)pyrene