Showing papers by "Frederica P. Perera published in 1986"

Biomonitoring of workers exposed to carcinogens: immunoassays to benzo(a)pyrene-DNA adducts as a prototype.

Abstract: A new tool for the study of occupational carcinogenesis is "molecular dosimetry" or biomonitoring to establish the biologically effective dose of carcinogens in workers. Human monitoring of biologically effective dose and preclinical response has the potential to flag the need for protective measures and/or surveillance. Comparable biologically effective dose and preclinical response data in humans and laboratory animals for whom tumor incidence is known can also enhance risk extrapolation between species. This paper will provide a brief overview of biomonitoring methods now under development, including advantages, limitations, applications to date, and research needs. Application to the monitoring of worker populations requires careful thought about the use to which monitoring data will be put.

New approaches in risk assessment for carcinogens.

Abstract: Methods are needed to improve the ability of biomonitoring and epidemiological studies to identify potential carcinogenic hazards and to quantify human risk. The limitations of pharmacokinetic models can be mitigated by the direct measurement of molecular markers of biologically effective dose of carcinogen. Parallel animal and human studies are recommended as a means of validating these markers.

Immunologic quantification of carcinogen-DNA adducts.

Abstract: 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. In general, all the antibodies have their highest reactivity with the original antigen and do not cross-react with the free carcinogens. Competitive ELISA with these antibodies can quantify modification levels with a sensitivity of about one adduct per 107-108 nucleotides. The antibodies are currently being used to measure adduct levels in animals exposed to carcinogens. In addition, DNA isolated from the lung, placenta, and pheripheral white blood cells of humans with various environmental exposures are being tested.