A 32P-Postlabeling method developed in the applicant's laboratory will be applied to study potential covalent DNA lesions in human white blood cells and tissues exposed to occupational or environmental mixtures of genotoxic compounds. The basic procedure entails the enzymatic digestion of the DNA preparation to be tested for the presence of adducts to deoxyribonucleoside 3'-monophosphates, conversion of these mononucleotides to 5'-32P-labeled deoxyribonucleoside 3',5'-bisphosphates, resolution of the 32P-labeled nucleotides by thin-layer chromatography, and autoradiography. 32P-Labeled adduct fractions are detected as extra spots on X-ray film and are quantitated by scintillation (Cerenkov) counting. Characteristic """"""""fingerprints"""""""" are obtained for DNA adducts formed in vivo from authentic carcinogens or mixtures of genotoxic compounds such as cigarette smoke. The 32P-postlabeling assay will be suitable specifically for the analysis of traces of adducts in microgram amounts of human DNA. For the characterization of adducts observed in human DNA, co-chromatography and stability studies will be conducted with adducts obtained from DNA of experimental animals treated with crude environmental/occupational mixtures or authentic carcinogens known to occur in the exposure of interest. Cigarette smoking will be considered as a confounding variable on the basis of the detection of specific smoking-associated DNA adducts. The project will focus on occupational exposures to polycyclic aromatic hydrocarbons, aromatic amines/amides, azo compounds, dyestuffs, formaldehyde, and styrene. In addition, it is proposed to study whether the exposure to emissions of wood-burning stoves and the natural process of aging give rise to adducts in human DNA.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA043263-01
Application #
3548867
Study Section
(SRC)
Project Start
1986-08-01
Project End
1990-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Reddy, M V; Hemminki, K; Randerath, K (1991) Postlabeling analysis of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells of foundry workers. J Toxicol Environ Health 34:177-85
Randerath, E; Randerath, K; Reddy, R et al. (1991) Induction of rat liver DNA alterations by chronic administration of peroxisome proliferators as detected by 32P-postlabeling. Mutat Res 247:65-76
Hemminki, K; Grzybowska, E; Chorazy, M et al. (1990) Aromatic DNA adducts in white blood cells of coke workers. Int Arch Occup Environ Health 62:467-70
Hemminki, K; Grzybowska, E; Chorazy, M et al. (1990) DNA adducts in human environmentally exposed to aromatic compounds in an industrial area of Poland. Carcinogenesis 11:1229-31
Hemminki, K; Grzybowska, E; Chorazy, M et al. (1990) DNA adducts in humans related to occupational and environmental exposure to aromatic compounds. IARC Sci Publ :181-92
Randerath, K; Li, D H; Randerath, E (1990) Age-related DNA modifications (I-compounds): modulation by physiological and pathological processes. Mutat Res 238:245-53
Reddy, M V; Kenny, P C; Randerath, K (1990) 32P-assay of DNA adducts in white blood cells and placentas of pregnant women: lack of residential wood combustion-related adducts but presence of tissue-specific endogenous adducts. Teratog Carcinog Mutagen 10:373-84
Yang, P F; Randerath, K (1990) High-resolution TLC mapping and characterization of 32P-postlabeled monophosphate 7,12-dimethylbenz[a]anthracene-DNA adducts. Carcinogenesis 11:159-64
Randerath, K; Randerath, E (1990) Monitoring carcinogen actions on DNA by 32P-postlabeling. Princess Takamatsu Symp 21:317-28
Reddy, M V; Randerath, K (1990) A comparison of DNA adduct formation in white blood cells and internal organs of mice exposed to benzo[a]pyrene, dibenzo[c,g]carbazole, safrole and cigarette smoke condensate. Mutat Res 241:37-48

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