||Use of Human Peripheral Blood Lymphocytes to Measure DNA Binding Capacity of Chemical Carcinogens.
Gupta, R. C. ;
Earley, K. ;
Sharma, S. ;
||Baylor Coll. of Medicine, Houston, TX. ;Roger Williams General Hospital, Providence, RI.;Health Effects Research Lab., Research Triangle Park, NC.
Deoxyribonucleic acids ;
Thin layer chromatography ;
DNA damage ;
Metabolic activation ;
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||Although animal models have been used successfully to study metabolic activation and binding of carcinogens to DNA, only limited studies have been done in human systems. To circumvent the problems associated with the inaccessibility of human tissues and a lack of sensitive methods to detect DNA damage, the study investigated the capability of human peripheral blood lymphocytes to metabolize carcinogens to their DNA binding species by a 32p-adduct assay. Freshly isolated lymphocytes were exposed at 37 C for 18 hr to 30 micro/M each of ten compounds known or suspected to be carcinogenic in experimental animals. Anthracene, pyrene, and perylene were included as noncarcinogen controls. 32p-postlabeling analysis of exposed DNAs showed exclusively or predominantly 1 major adduct for all test carcinogens, except for 2-anthramine (AA), triphenylene, and 7, 12-dimethylbenzanthracene (DMBA), which showed 2-3 adducts, in the range of 8-1500 atto(a)mol/micrograms DNA. No DNA binding was detected for the noncarcinogens. From 12 specimens studied thus far, significant interindividual variations were observed for 2-aminofluorene (62-fold), DMBA (10-fold) benzidine (19-fold) and 1,2-benzanthracene (18-fold) in their capacity to bind to the lymphocyte DNA. These data indicate that all test carcinogens formed low but readily measurable levels of DNA adducts.
||Pub. in Proceedings of the National Academy of Science, v85 p3513-3517 May 88. Prepared in cooperation with Roger Williams General Hospital, Providence, RI. Sponsored by Health Effects Research Lab., Research Triangle Park, NC.
|NTIS Title Notes
||Reprint: Use of Human Peripheral Blood Lymphocytes to Measure DNA Binding Capacity of Chemical Carcinogens.
||PC A02/MF A01