We shall further develop and apply a 32P-labeling test recently developed by us to detect covalent adducts formed by the reaction of nucleic acids (DNA and, to a lesser extent, RNA) with chemicals. The test involves (i) the reaction of DNA with chemical(s) in vitro or in vivo; (ii) DNA purification; (iii) enzymatic digestion of DNA to deoxynucleoside 3'-monophosphates; (iv) conversion of the latter to 32P-labeled deoxynucleoside 3',5'-bisphosphates by incubation with [Gamma-32P]ATP and T4 polynucleotide kinase; (v) fingerprinting of the 32P-labeled digests by reversed-phase high-performance liquid chromatography and anion-exchange thin-layer chromatorgraphy on polyethyleneimine-cellulose, and (vi) autoradiography. Adducts formed by the covalent binding to DNA of chemical are detected as extra spots on such fingerprints. A similar procedure applies to treatment and analysis of RNA. The test will be applied to carcinogenic alkylating agents, mycotoxins, aminoazo dyes, aromatic amines and amides, polycyclic aromatic hydrocarbons, other aromatics, nitrosamines, chlorinated hydrocarbons, hydrazine derivatives, and antineoplastic agents. A number of noncarcinogens will also be assayed. The results will be compared with published data from mutagenesis and carcinogenesis assays to determine the scope of the test as a prescreen for carcinogens.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
Zhou, Guo-Dong; Moorthy, Bhagavatula; Bi, Jia et al. (2007) DNA adducts from alkoxyallylbenzene herb and spice constituents in cultured human (HepG2) cells. Environ Mol Mutagen 48:715-21
Zhou, Guo-Dong; Randerath, Kurt; Donnelly, Kirby C et al. (2004) Effects of NQO1 deficiency on levels of cyclopurines and other oxidative DNA lesions in liver and kidney of young mice. Int J Cancer 112:877-83
Randerath, K; Zhou, G D; Somers, R L et al. (2001) A 32P-postlabeling assay for the oxidative DNA lesion 8,5'-cyclo-2'-deoxyadenosine in mammalian tissues: evidence that four type II I-compounds are dinucleotides containing the lesion in the 3' nucleotide. J Biol Chem 276:36051-7
Zhou, G D; Randerath, E; Randerath, K (2001) Effects of dietary transition metals on oxidative DNA lesions in neonatal rats. Mutat Res 479:71-9
Moorthy, B (2000) Persistent expression of 3-methylcholanthrene-inducible cytochromes P4501A in rat hepatic and extrahepatic tissues. J Pharmacol Exp Ther 294:313-22
Zhou, G; Hernandez, N S; Randerath, E et al. (2000) Effects of different diets and dietary restriction on perinatal endogenous DNA adducts. Time dependence of oxidative and presumptive nonoxidative lesions. Mutat Res 447:137-47
Zhou, G D; Hernandez, N S; Randerath, E et al. (1999) Acute elevation by short-term dietary restriction or food deprivation of type I I-compound levels in rat liver DNA. Nutr Cancer 35:87-95
Chung, F L; Nath, R G; Nagao, M et al. (1999) Endogenous formation and significance of 1,N2-propanodeoxyguanosine adducts. Mutat Res 424:71-81
Randerath, K; Randerath, E; Zhou, G D et al. (1999) Genotoxicity of complex PAH mixtures recovered from contaminated lake sediments as assessed by three different methods. Environ Mol Mutagen 33:303-12
Randerath, K; Randerath, E; Zhou, G D et al. (1999) Bulky endogenous DNA modifications (I-compounds) -possible structural origins and functional implications. Mutat Res 424:183-94

Showing the most recent 10 out of 113 publications