Effect of polychlorinated biphenyls (Aroclor 1254) on inducible and repressible microsomal N-demethylases in the mouse and rat.

A comparative study of the effects of the polychlorinated biphenyl mixture Aroclor 1254, 3-methylcholanthrene, and starvation on hepatic dimethylnitrosamine (DMN) demethylase (a repressible enzyme) and azo dye N-demethylase (an inducible enzyme) has been carried out. As previously observed with polycyclic hydrocarbons and phenobarbital, Aroclor in rats is a potent inducer of liver tissue proliferation and of azo dye N-demethylase. However, in mice, although the inducing effect on liver tissue proliferation and azo dye N-demethylase activity is maintained, there is no change in DMN demethylase activity as a result of Aroclor administration. As in rats, 3-methylcholanthrene induces the azo dye N-demethylase in mice. This hydrocarbon, which is known to substantially repress the DMN demethylase in rats, has, however, no effect on this enzyme in mice. While starvation is known to have a substantial inducing effect on DMN demethylase in rats, in mice starvation brings about a moderate induction of DMN demethylase.

[1]  N. Venkatesan,et al.  Repression of dimethylnitrosamine-demethylase by typical inducers of microsomal mixed-function oxidases. , 1975, Biochemical pharmacology.

[2]  B. Brodie,et al.  Reduction by pretreatment with dibenamine of hepatotoxicity induced by carbon tetrachloride, thioacetamide or dimethylnitrosamine. , 1975, Toxicology and applied pharmacology.

[3]  K. Hirao,et al.  Inhibitory effect of polychlorinated biphenyls on liver tumorigenesis in rats treated with 3'-methyl-4-dimethylaminoazobenzene, n-2-fluorenylacetamide, and diethylnitrosamine. , 1974, Journal of the National Cancer Institute.

[4]  I. Sipes,et al.  Dibenamine impairment of rat hepatic microsomal enzymes and its relation to hepatotoxicity induced by CCl4 and dimethylnitrosamine. , 1974, Drug metabolism and disposition: the biological fate of chemicals.

[5]  J. Ward,et al.  Dibenamine: selective protection against diethylnitrosamine-induced hepatic carcinogenesis but not oral, pharyngeal and esophageal carcinogenesis. , 1974, Toxicology and applied pharmacology.

[6]  D. Hadjiolov,et al.  Effect of aminoacetonitrile on the metabolism of dimethylnitrosamine and methylation of RNA during liver carcinogenesis. , 1974, Journal of the National Cancer Institute.

[7]  S. Aust,et al.  Multiplicity of cytochrome P450 hemoproteins in rat liver microsomes. , 1974, Biochemical and biophysical research communications.

[8]  H. Popper,et al.  Microsomal metabolism of dimethylnitrosamine and the cytochrome P-450 dependency of its activation to a mutagen. , 1973, Cancer research.

[9]  K. Comai,et al.  Existence and separation of three forms of cytochrome P-450 from rat liver microsomes. , 1973, The Journal of biological chemistry.

[10]  D. Bickers,et al.  Polychlorinated biphenyls: a new type of inducer of cytochrome P-448 in the liver. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Hadjiolov,et al.  Effect of aminoacetonitrile on the fine structure and cytochemistry of hepatic cells in rats fed two carcinogenic N-nitrosodialkylamines. , 1973, Journal of the National Cancer Institute.

[12]  H. Popper,et al.  Mutagenicity of Primary and Secondary Carcinogens Altered by Normal and Induced Hepatic Microsomes 1 , 1973, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[13]  A. Conney,et al.  Protection against dimethylnitrosamine toxicity by pregnenolone-16 -carbonitrile. , 1972, Nature: New biology.

[14]  D. Bickers,et al.  Polychlorinated biphenyls: comparative effects of high and low chlorine containing Aroclors on hepatic mixed function oxidase. , 1972, Research communications in chemical pathology and pharmacology.

[15]  N. Venkatesan,et al.  Induction and repression of microsomal drug-metabolizing enzymes by polycyclic hydrocarbons and phenobarbital: theoretical models. , 1971, Journal of theoretical biology.

[16]  P. Magee,et al.  Cellular injury and carcinogenesis. Inhibition of metabolism of dimethylnitrosamine by aminoacetonitrile. , 1970, The Biochemical journal.

[17]  N. Venkatesan,et al.  Mechanism of 3-methylcholanthrene-induced inhibition of dimethylnitrosamine demethylase in rat liver. , 1970, Cancer research.

[18]  N. Venkatesan,et al.  Amino acid induction and carbohydrate repression of dimethylnitrosamine demethylase in rat liver. , 1970, Cancer research.

[19]  N. Venkatesan,et al.  Differential effect of polycyclic hydrocarbons on the demethylation of the carcinogen dimethylnitrosamine by rat tissues. , 1968, Life sciences.

[20]  E. Bresnick,et al.  Microsomal N-demethylase activity in developing rat liver after administration of 3-methylcholanthrene. , 1968, Biochemical pharmacology.

[21]  C. Hoch‐Ligeti,et al.  Combined carcinogenic effects of dimethylnitrosamine and 3-methylcholanthrene in the rat. , 1968, Journal of the National Cancer Institute.

[22]  K. Jervell,et al.  Studies on the 3-methylcholanthrene induction and carbohydrate repression of rat liver dimethylaminoazobenzene reductase. , 1965, Archives of biochemistry and biophysics.

[23]  H. Pitot,et al.  STUDIES ON THE INDUCTION AND REPRESSION OF ENZYMES IN RAT LIVER. II. CARBOHYDRATE REPRESSION OF DIETARY AND HORMONAL INDUCTION OF THREONINE DEHYDRASE AND ORNITHINE DELTA-TRANSAMINASE. , 1964, The Journal of biological chemistry.

[24]  J. Young,et al.  METABOLIC CONTROL OF ENZYMES INVOLVED IN LIPOGENESIS AND GLUCONEOGENESIS. , 1964, Biochemistry.

[25]  D. Tschudy,et al.  The effect of carbohydrate feeding on the induction of δ-aminolevulinic acid synthetase , 1964 .

[26]  A. Conney,et al.  Induction of microsomal enzyme synthesis by polycyclic aromatic hydrocarbons of different molecular sizes. , 1961, The Journal of biological chemistry.

[27]  A. Conney,et al.  Adaptive increases in drug-metabolizing enzymes induced by phenobarbital and other drugs. , 1960, The Journal of pharmacology and experimental therapeutics.

[28]  J. Miller,et al.  The metabolism of methylated aminoazo dyes. V. Evidence for induction of enzyme synthesis in the rat by 3-methylcholanthrene. , 1956, Cancer research.

[29]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[30]  J. Miller,et al.  THE CARCINOGENICITY OF CERTAIN DERIVATIVES OF p-DIMETHYLAMINOAZOBENZENE IN THE RAT , 1948, The Journal of experimental medicine.

[31]  M. Goerner,et al.  The Effect of Dibenzanthracene on the Liver , 1939 .

[32]  A. White,et al.  Inhibition of growth of the rat by oral administration of methylcholanthrene, benzpyrene, or pyrene, and the effects of various dietary supplements. , 1939 .

[33]  A. Conney,et al.  Factors Influencing Drug Metabolism , 1962 .