The proposed research centers about the metabolism and disposition of xenobiotic chemicals in fish. The major goals are to determine the pathways of biotransformation of chlorinated benzenes, pyrethroid insecticides and petroleum hydrocarbons in fish and to determine the extent to which metabolism influences the toxicity and persistence of these chemicals. If biotransformation of these compounds in fish leads to less toxic compounds and the reactions proceed at significant rates, inhibition of their metabolism would be expected to increase toxicity as well as alter residue patterns of the parent compound and metabolites. On the other hand stimulation of metabolism by inducers such as polychlorinated biphenyls and polycyclic aromatic hydrocarbons may decrease toxicity and increase residues of metabolites. The information gleaned from these biotransformation studies may lead to the mechanisms of species selectivity of many water borne pollutants in addition to providing data necessary for residue analysis of metabolites of foreign compounds as well as the parent molecule. In general, the experimental approach involves determination of the acute toxicity (LC50) of the above compounds in trout, studying the metabolism of each compound and determining if the toxicity is altered by known inhibitors and inducers of microsomal drug metabolizing enzymes. Special attention will be given to the possibility of alteration of these metabolic processes by inducers and inhibitors which may be present in the aqueous environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES001080-12
Application #
3249485
Study Section
Toxicology Study Section (TOX)
Project Start
1978-06-01
Project End
1988-05-31
Budget Start
1986-06-01
Budget End
1987-05-31
Support Year
12
Fiscal Year
1986
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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