Individual values of excretion of benzo[a]pyrene metabolites and susceptibility to its carcinogenic effect in rats.

In white outbred LIO rats exposed to multiple intraperitoneal (i.p.) doses (10 mg/kg) of benzo[a]pyrene (BP) in the form of a water-lipid emulsion, individual peculiarities of the excretion of its metabolites, BP-7,8-diol and 3-hydroxy-BP (3-OH-BP) in urine and feces were detected and compared with the carcinogenic effect. Parameters of BP metabolite excretion differed from those found in our previous experiments with rats exposed to single high i.p. doses of BP (100 and 200 mg/kg), dissolved in sunflower oil [11,12]. In comparison with our previous observation, in the present study, the carcinogenic effect was considerably weaker (5/22 versus 10/19). The rats that developed tumours of internal tissues (four peritoneal malignant histiocytomas and one lung lymphosarcoma), excreted higher quantities of BP-7,8-diol in the urine than other rats. The possible implication of monitoring excretion of BP metabolites for predicting individual susceptibility to its carcinogenic effect is discussed.

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.

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.