Abstract

The long-term goal of this project is to identify and characterize the molecular mechanisms by which chemicals induce tumors. Attention is focused on better understanding the role of altered nucleic acids in this process. Primary efforts are directed towards the aromatic amines. Since these carcinogens must undergo metabolic activation in order to react with tissue macromolecules, the identification and characterization of these pathways are specific aims of this project. The transient nature of the reactive species involved dictates that the responsive tissues be the targets of the investigation. Within this context, specific attention is beng given, but not limited to, those enzymes that can generate these reactive and, consequently, unstable products from arylhydroxamic acids by N,O-acyltransfer. Knowledge of these acyl-specific enzymes is being utilized in intact cell and tumor induction experiments that are designed to explore the biological importance of these pathways.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA023386-11
Application #
3166130
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1978-04-01
Project End
1989-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
11
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Barbara Ann Karmanos Cancer Institute
Department
Type
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48201

  Publications

Soos, Gyorgyike; Haas, Gabriel P; Wang, Ching Y et al. (2003) Differential gene expression in human prostate cancer cells adapted to growth in bone in Beige mice. Urol Oncol 21:15-9
Wang, Ching Y; Jones, Richard F; Debiec-Rychter, Maria et al. (2002) Correlation of the genotypes for N-acetyltransferases 1 and 2 with double bladder and prostate cancers in a case-comparison study. Anticancer Res 22:3529-35
Archer, C L; Morse, P; Jones, R F et al. (2000) Carcinogenicity of the N-hydroxy derivative of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3, 8-dimethyl-imidazo[4,5-f]quinoxaline and 3, 2'-dimethyl-4-aminobiphenyl in the rat. Cancer Lett 155:55-60
Singh, A; Jones, R F; Friedman, H et al. (1999) Expression of p53 and pRb in bladder and prostate cancers of patients having both cancers. Anticancer Res 19:5415-7
Archer, C; Debiec-Rychter, M; Morse, P et al. (1999) Epithelial proliferation and expression of the aromatic amine activation enzyme N-acetyltransferase in the prostate of postnatal rat. Anticancer Res 19:4013-6
Vosianov, A F; Romanenko, A M; Zabarko, L B et al. (1999) Prostatic intraepithelial neoplasia and apoptosis in benign prostatic hyperplasia before and after the Chernobyl accident in Ukraine. Pathol Oncol Res 5:28-31
Wang, C Y; Debiec-Rychter, M; Schut, H A et al. (1999) N-Acetyltransferase expression and DNA binding of N-hydroxyheterocyclic amines in human prostate epithelium. Carcinogenesis 20:1591-5
Debiec-Rychter, M; Tada, M; Poirier, M C et al. (1998) DNA adduct formation in human and rat mammary epithelium by N-hydroxy derivatives of 2-aminofluorene and 4-aminobiphenyl. Teratog Carcinog Mutagen 18:35-9
Soos, G; Jones, R F; Haas, G P et al. (1997) Comparative intraosseal growth of human prostate cancer cell lines LNCaP and PC-3 in the nude mouse. Anticancer Res 17:4253-8
Hirose, M; Shirai, T; Lee, M S et al. (1997) Carcinogenecity of the N-acyl derivatives of N-hydroxy-trans-4-aminostilbene in CD rats. Chem Biol Interact 106:123-32

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