Immunologic quantification of carcinogen-DNA adducts.
Sensitive immunological methods for the detection of carcinogen-DNA adducts have recently been developed. These techniques are particularly useful for screening human populations for exposure to environmental carcinogens. Measurement of the biologically effective dose in humans may be useful in detecting carcinogenic hazards and carrying out risk estimates. We have developed monoclonal antibodies to several carcinogen-DNA adducts. These have included DNA modified by a benzo[a]pyrene diol epoxide (BPDE-I), 1-aminopyrene (1-AP) and 8-methoxypsoralen (8-MOP). BALB/cCr mice were immunized with the modified DNAs complexed electrostatically to methylated bovine serum albumin. Several stable clones have been isolated for each of the modified DNAs and characterized by enzyme-linked immunosorbent assay (ELISA). All antibodies are highly specific for the appropriate modified DNA and do not cross-react with nonmodified DNA. The antibodies to BPDE-I-DNA have significant cross-reactivity with DNAs modified by similar antitrans diol epoxides of benz[a]anthracene and chrysene. These DNAs all contain N-2 of guanine adducts. The antibody probably recognizes a shared determinant encompassing the guanine base and the hydrocarbon ring containing the hydroxide groups. The antibodies cross-react with BPDE-I-dG, the monoadduct isolated from DNA, but with lower sensitivity than for the intact modified DNA. They do not react with acetylaminofluorene (AAF) or 1-AP modified DNA, both of which contain C-8 of guanosine adducts. The antibodies to 1-AP-modified DNA demonstrate cross-reactivity with 8-nitro-1-aminopyrene- and 6-nitro-1-aminopyrene-modified DNA, as well as some slight cross-reactivity with BPDE-I-DNA and AAF-DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000032:analysis; D001580:Benzopyrenes / Q000032:analysis; D002273:Carcinogens / Q000032:analysis*; D003429:Cross Reactions; D004247:DNA / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D008730:Methoxsalen / Q000032:analysis; D011721:Pyrenes / Q000032:analysis
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001580:Benzopyrenes; D002273:Carcinogens; D011721:Pyrenes; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; C004482:1-aminopyrene; D008730:Methoxsalen