This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huh, N.-h. Articles by Kuroki, T. Search for Related Content PubMed PubMed Citation Articles by Huh, N.-h. Articles by Kuroki, T.

Immunoanalytical Detection of O⁴-Ethylthymine in Liver DNA of Individuals with or without Malignant Tumors¹

Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108 [N. H., M. S. S., T. K.], Japan; Department of Pathology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113 [J. S.], Japan; and Institut für Zellbiologie (Tumorforschung), Universitat Essen (GH), D-4300 Essen 1 [M. F. R.], Federal Republic of Germany

The detection and quantitation of carcinogen-DNA adducts in human cells are the key parameters in the molecular dosimetry of human exposure to environmental carcinogens. For investigating the possible relevance of alkylating N-nitroso compounds as causative agents in human carcinogenesis, we have quantitated O⁴-ethyl-2'-deoxythymidine (O⁴-EtdThd) in human liver DNA obtained from 33 autopsy specimens, i.e., 13 cases with primary liver cancer (LC), 8 with cancers other than liver cancer (OC), and 12 with noncancerous diseases (NC). None of the cases analyzed had a history of known occupational exposure to ethylating agents. The detection limit for O⁴-EtdThd was 3 x 10^-8 as a O⁴-EtdThd/dThd molar ratio in DNA, which was attained by the combination of prefractionation of DNA hydrolysates (= 20 mg of DNA/sample) by high performance liquid chromatography and competitive radioimmunoassay using anti-(O⁴-EtdThd) monoclonal antibody ER-01. Except for one case in each group, O⁴-EtdThd [or, alternatively, (an) unidentified structural modification(s) of DNA recognized by monoclonal antibody ER-01] was detected at mean (± SD) O⁴-EtdThd/dThd molar ratios of 39.9 ± 40.2 x 10^-8, 53.5 ± 74.0 x 10^-8, and 11.7 ± 6.5 x 10^-8, respectively, in LC, OC, and NC. The difference of the O⁴-EtdThd content in DNA between LC and NC, or between LC + OC and NC, was statistically significant at P < 0.05. These results suggest that humans are exposed to ethylating agents in vivo and that a premutagenic DNA lesion (O⁴-EtdThd) eventually accumulates in DNA, possibly to a biologically significant extent.

¹ This work was supported in part by grants for Cancer Research and for Special Project Research, Cancer-Bioscience from the Ministry of Education, Science and Culture of Japan and by the Deutsche Forschungsgemeinschaft (SFB 102/A7).

² To whom requests for reprints should be addressed, at the Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108, Japan.

Received 6/27/88. Revised 9/19/88. Accepted 9/30/88.

This article has been cited by other articles:

				A. C. Povey DNA Adducts: Endogenous and Induced Toxicol Pathol, May 1, 2000; 28(3): 405 - 414. [Abstract] [PDF]

				R. M. Santella Immunological Methods for Detection of Carcinogen-DNA Damage in Humans Cancer Epidemiol. Biomarkers Prev., September 1, 1999; 8(9): 733 - 739. [Full Text]