Abstract

Humans are constantly exposed to the vast mixture of chemicals that are present in the environment. Often this mixture contains both carcinogenic polcyclic aromatic hydrocarbons and other types of hydrocarbons and chemicals that have cocarcinogenic and/or tumor-promoting activity (i.e., urban air, cigarette smoke, ect.). To determine how combined exposure may influence the effects of carcinogens, the modification induced by cocarcinogens and tumor promoters in the metabolic activation, detoxification, DNA interactions and biological effects of polycyclic aromatic hydrocarbons will be measured in hamster embroyo cell cultures. The production of water-soluble glucuronic acid conjugates of hydrocarbon metabolites will also be measurd and the role of these conjugates in the induction of biological effects by hydrocarbons will be investigated. The results obtained should aid in predicting the effects of exposure to carcinogenic chemicals in the presence of tumor promoters, cocarcinogens and mixtures of both, and, thereby, permit modification of these effects. The studies on glucuronic acid conjugate formation will help in interpreting the results of in vitro transformation assays when they used to screen for carcinogens and may lead to the development of assays with enhanced sensitivity for the detection of carcinogens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA028825-10
Application #
3482125
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1980-06-01
Project End
1991-05-31
Budget Start
1989-06-01
Budget End
1990-05-31
Support Year
10
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Purdue University
Department
Type
Schools of Pharmacy
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907

  Publications

Hooven, Louisa Ada; Baird, William M (2008) Proteomic analysis of MCF-7 cells treated with benzo[a]pyrene, dibenzo[a,l]pyrene, coal tar extract, and diesel exhaust extract. Toxicology 249:1-10
Courter, Lauren A; Musafia-Jeknic, Tamara; Fischer, Kay et al. (2007) Urban dust particulate matter alters PAH-induced carcinogenesis by inhibition of CYP1A1 and CYP1B1. Toxicol Sci 95:63-73
Mahadevan, Brinda; Luch, Andreas; Atkin, Jennifer et al. (2007) Inhibition of human cytochrome p450 1b1 further clarifies its role in the activation of dibenzo[a,l]pyrene in cells in culture. J Biochem Mol Toxicol 21:101-9
Miranda, C L; Chung, W G; Wang-Buhler, J-L et al. (2006) Comparative in vitro metabolism of benzo[a]pyrene by recombinant zebrafish CYP1A and liver microsomes from beta-naphthoflavone-treated rainbow trout. Aquat Toxicol 80:101-8
Baird, William M; Hooven, Louisa A; Mahadevan, Brinda (2005) Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action. Environ Mol Mutagen 45:106-14
Reliene, Ramune; Hlavacova, Alexandra; Mahadevan, Brinda et al. (2005) Diesel exhaust particles cause increased levels of DNA deletions after transplacental exposure in mice. Mutat Res 570:245-52
Musafia-Jeknic, Tamara; Mahadevan, Brinda; Pereira, Clifford et al. (2005) Long-term effects of a standardized complex mixture of urban dust particulate on the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons in human cells in culture. Toxicol Sci 88:358-66
Mahadevan, Brinda; Luch, Andreas; Bravo, Claudia F et al. (2005) Dibenzo[a,l]pyrene induced DNA adduct formation in lung tissue in vivo. Cancer Lett 227:25-32
Hooven, Louisa A; Mahadevan, Brinda; Keshava, Channa et al. (2005) Effects of suberoylanilide hydroxamic acid and trichostatin A on induction of cytochrome P450 enzymes and benzo[a]pyrene DNA adduct formation in human cells. Bioorg Med Chem Lett 15:1283-7
Mahadevan, Brinda; Marston, Charis P; Dashwood, Wan-Mohaiza et al. (2005) Effect of a standardized complex mixture derived from coal tar on the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons in human cells in culture. Chem Res Toxicol 18:224-31

Showing the most recent 10 out of 46 publications