During the previous projects period, the biotransformation and fate of xenobiotic chemicals in fish have been intensively studied. The induction of trout hepatic monooxygenases by chemicals and the influence of induction on bioaccumulation of chemicals has been the subject of recent investigations. During the last two years, a cDNA which codes for the hydrocarbon-inducible form of hepatic P1-450 has been developed and the studies in this proposal are designed to further characterize this cDNA and investigate its possible use in an assay to detect exposure of fish to hazardous chemicals in water supplies. This assay could serve as a sentinel in monitoring water for chemicals which could adversely affect human health. The model inducers to be studied include 3- methylcholanthrene (3-MC), beta-naphthoflavone (BNF), 2,3,7,8- tetrachlorodibenzodioxin (TCDD) and 2,3,7,8-tetra- chlorodibenzofuran (TCDF). A second goal in this proposal is to isolate and characterize the forms of P-450 which are present in fish liver and to determine the nature of the biotransformation products they form from specific chemicals. These metabolic products may accumulate in fish destined for human consumption and may differ from those formed in mammalian tissues if the P-450 isozyme profile of fish liver is different from that found in mammals. The chemicals to be studied include chlordimeform, fenitrothion, aldicarb and N- acetylaminofluorene.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES001080-17
Application #
3249489
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1978-06-01
Project End
1993-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
17
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Haasch, M L; Graf, W K; Quardokus, E M et al. (1994) Use of 7-alkoxyphenoxazones, 7-alkoxycoumarins and 7-alkoxyquinolines as fluorescent substrates for rainbow trout hepatic microsomes after treatment with various inducers. Biochem Pharmacol 47:893-903
Lee, P C; Yoon, H I; Haasch, M L et al. (1993) Negative control of cytochrome P450 1A1 (CYP1A1) by glucocorticoids in rainbow trout liver. Comp Biochem Physiol C 104:457-61
Haasch, M L; Quardokus, E M; Sutherland, L A et al. (1993) Hepatic CYP1A1 induction in rainbow trout by continuous flowthrough exposure to beta-naphthoflavone. Fundam Appl Toxicol 20:72-82
Haasch, M L; Sutherland, L A; Wejksnora, P J et al. (1992) Effect of acrylamide monomer on hepatic CYP1A1 monooxygenase induction in rainbow trout. Comp Biochem Physiol C 102:281-6
Stegeman, J J; Lech, J J (1991) Cytochrome P-450 monooxygenase systems in aquatic species: carcinogen metabolism and biomarkers for carcinogen and pollutant exposure. Environ Health Perspect 90:101-9
Waddell, W J; Lech, J J; Marlowe, C et al. (1990) The distribution of [14C]acrylamide in rainbow trout studied by whole-body autoradiography. Fundam Appl Toxicol 14:84-7
Haasch, M L; Wejksnora, P J; Stegeman, J J et al. (1989) Cloned rainbow trout liver P(1)450 complementary DNA as a potential environmental monitor. Toxicol Appl Pharmacol 98:362-8
Erickson, D A; Goodrich, M S; Lech, J J (1988) The effect of piperonyl butoxide on hepatic cytochrome P-450-dependent monooxygenase activities in rainbow trout (Salmo gairdneri). Toxicol Appl Pharmacol 94:1-10
Haasch, M L; Kleinow, K M; Lech, J J (1988) Induction of cytochrome P-450 mRNA in rainbow trout: in vitro translation and immunodetection. Toxicol Appl Pharmacol 94:246-53
Petersen, D W; Cooper, K R; Friedman, M A et al. (1987) Behavioral and histological effects of acrylamide in rainbow trout. Toxicol Appl Pharmacol 87:177-84

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