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Molecular Pharmacology, Vol 18, 559-564, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Hepatic Glutathione Transferase Activity Induced by Polycyclic Aromatic Compounds

Lack of Correlation with the Murine Ah Locus

JAMES S. FELTON 1, JEANNE N. KETLEY 2, WILLIAM B. JAKOBY 2, ANTERO AITIO 3, JOHN R. BEND 3, and DANIEL W. NEBERT 1

1 Developmental Pharmacology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20205
2 Laboratory of Biochemistiy and Metabolism, National Institute of Arthritis, Metabolism and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20205
3 Laboratory of Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Hepatic cytosolic glutathione transferase activity with 1-chloro-2,4-dinitrobenzene as substrate was induced by 3-methylcholanthrene or beta-naphthoflavone in C57BL/6N inbred mice and in (C57BL/6N)(DBA/2N)F1 but not in DBA/2N inbred mice. High doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin induced the transferase activity in both C57BL/6N and DBA/2N mice. The glutathione transferase activity with benzo[a]pyrene 4,5-oxide as substrate was induced by 3-methylcholanthrene in C57BL/6N but not DBA/2N mice. The transferase activity with styrene 7,8-oxide as substrate was different from either of the above activities in that about twofold induction by 3-methylcholanthrene occurred in both C57BL/6N and DBA/2N mice. Among progeny from the (C57BL/6N)(DBA/2N)F1 x DBA/2N backcross, however, no association was found between the transferase induction process by 3-methylcholanthrene and the presence of the Ah receptor [i.e., inducible aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity]. It is therefore concluded that induction of glutathione transferase activity by polycyclic aromatic compounds is mediated by a gene(s) distinct from the Ah regulatory genes. These data emphasize the importance of examining progeny from the appropriate backcross before making conclusions about the genetic linkage of any two expressed traits.

Note:
ACKNOWLEDGMENTS We thank Dr. William H. Habig for valuable discussions concerning the early portions of this work. The valuable technical help of Ms. Nancy M. Jensen and the expert secretarial assistance of Ms. Ingrid E. Jordan are also greatly appreciated.

Submitted on February 6, 1980
Accepted on June 11, 1980






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