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© 1992 Oxford University Press

research-article

Determination of human exposure to the dietary carcinogen 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) from hemoglobin adduct: the relationship to DNA adducts

Atsushi Umemoto 1 2, Yasumasa Monden 2, Spiros Grivas 1 3, Katsumi Yamashita 1 4 and Takashi Sugimura 1 5

1Biochemistry Division, National Cancer Center Research Institute Tsukiji, Chuo-ku, Tokyo 104
2The Second Department of Surgery, University of Tokushima, School of Medicine Tokushima 770, Japan
3Present address: Department of Chemistry, Swedish University of Agricultural Science P.O. Box 7015, S-750 07, Uppsala, Sweden
4Present address: Department of Molecular Biology. Graduate School of Medical Science, Kyushu University Fukuoka 812, Japan

5To whom all correspondence should be sent

A quantitative method for estimation of the exposure of the food-borne carcinogen, 3-amino-1,4-dimethyl-5H-pyrldo-[4,3-b]indole (Trp-P-1), was developed by the analysis of its hemoglobin binding in rats. This method was then applied to show the presence of Trp-P-1—hemoglobin adducts in human blood. In rat experiments, 0.2 and 0.07% of the administered [14C]Trp-P-1 formed stable covalent adducts with blood hemoglobin and plasma proteins respectively. Subsequent strong acidic treatment (6 N HCI, 110°C, 24 h) of the Trp-P-1 — hemoglobin adducts cleaved peptide bonds of globin, and yielded mainly three derivatives of Trp-P-1. One of them (TPHB) represented ~50% of the total Trp-P-1 — hemoglobin adducts and was suitable for detection through its strong fluorescence. TPHB was used as a surrogate marker of the Trp-P-1—hemoglobin adducts. Linear dose dependency of Trp-P-1 binding to liver DNA and hemoglobin in rats was confirmed by 32P-postlabeling analysis and TPHB assay. The absence of Trp-P-1-DNA adducts and TPHB in nontreated rats was also confirmed. Using TPHB as a tool for human dosimetry of Trp-P-1, human blood samples from four healthy individuals were examined. TPHB was detected in all samples ranging from 0.23 to 4.33 pmol/g hemoglobin. These results suggest human exposure to Trp-P-1, probably from cooked foods or cigarette smoke, and its possible relationship to human carcinogenesis.


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