Enzymic and electrophoretic characterization of the hexachlorobenzene-induced cytochrome P-450 in the liver of rat

Vizethum, W.; Burkhardt, F; Goerz, G.

doi:10.3109/00498258009033740

Cited by 18 publications

(9 citation statements)

References 29 publications

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“…In the present investigation, however, it was not possible to demonstrate an alteration in the wavelength maximum of cytochrome P-450 or an increase in the MC-inducible AHH activity by OCS or by HCB. This is in contrast to several reports stating that HCB is a mixed type ofinducer giving a pattern similar to the sum of the effects of PB-and MC-type of inducers (Stonard 1975;Goldstein et al 1978;Vizethum et a/. 1980).…”

Section: Discussioncontrasting

confidence: 99%

“…1980;Parkinson et al 1980). HCB administration is reported to decrease the wavelength maximum of the reduced CO-bound cytochrome in some, (Stonard 1975) but not all, instances (Carlson 1978), as well as increase the activities of AHH (Goldstein et al 1978) and biphenyl 2-hydroxylase, another MC-inducible monooxygenase activity (Vizethum et at. 1980).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of Liver Microsomal Cytochrome P‐450 and Associated Monooxygenases by Octachlorostyrene in the Rat

Holme¹,

Dybing²

1982

Acta Pharmacologica et Toxicologica

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The inducing effects of octachlorostyrene (OCS) and hexachlorobenzene (HCB), chlorinated hydrocarbon contaminants found in fish, o n the microsomal cytochrome P-450 system were studied in rats. Administration of single doses of OCS and HCB at 50mg/kg intraperitoneally and higher led to increases in microsomal protein and cytochrome P-450 content, cytochrome P-450 reductase, ethylmorphine Ndemethylase, 4-nitroanisole O-demethylase, acetanilide 4-hydroxylase, but not in benzo(a)pyrene hydroxylase activities. Similar patterns of induction were seen after 14 days repeated intraperitoneal or oral dosing. Sodiumdodecylsulfate polyacrylamide gel electrophoresis of microsomes from OCS and HCB treated rats showed increases in proteins similar to those found after phenobarbital (PB) induction. Under the present experimental conditions OCS and HCB were found to be PB-type inducers.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Induction of Liver Microsomal Cytochrome P‐450 and Associated Monooxygenases by Octachlorostyrene in the Rat

Holme¹,

Dybing²

1982

Acta Pharmacologica et Toxicologica

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“…Over the years there has been some controversy regarding the type of induction of P-450 isozymes elicited by administration of hexachlorobenzene, a wide-spread environmental pollutant known to increase xenobiotic metabolism (9)(10)(11)(12)(13)(14)(15)(16) and cause porphyria in rodents and man (17,18) and cancer in mice (19) and hamsters (20). Some studies suggested that HCB is a PB-type inducer (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…Some studies suggested that HCB is a PB-type inducer (9)(10)(11). Other studies indicated that HCB is a "mixed-type'' inducer, inducing enzymatic activities indicative of both PB and 3-MC isozymes (12)(13)(14)(15)(16). Surprisingly, studies have shown that a number of lower chlorinated benzenes appear to induce a different pattern of cytochrome P-450-dependent enzymes than HCB does (15,16).…”

Section: Introductionmentioning

confidence: 99%

Induction of cytochrome P‐450 isozymes by hexachlorobenzene in rats and aromatic hydrocarbon (Ah)—Responsive mice

Linko¹,

Yeowell²,

Gasiewicz³

et al. 1986

J. Biochem. Toxicol.

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Hexachlorobenzene (HCB) differs markedly from other chlorinated benzenes (CBs) as an inducer of cytochrome P-450 (P-450) isozymes as determined by radioimmunoassay and immunoblotting. At greater than 99% pure, HCB induced both the phenobarbital-inducible forms, cytochromes P-450b + e (70 chi), and the 3-methylcholanthrene-inducible forms, cytochromes P-450c (58 chi) and P-450d (8 chi), in rat liver microsomes. The concentration of P-450d was considerably greater than that of P-450c in HCB-induced rat liver. In contrast to HCB, all lower chlorinated benzenes tested were PB-type inducers. Hexachlorobenzene increased the amounts of translatable messenger RNAs (mRNAs) for P-450b, P-450c, and P-450d in rat liver polysomes, suggesting that it increases the synthesis of these proteins. Evidence that HCB interacted with the putative Ah receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was equivocal. Western blots of liver microsomes from Ah-responsive C57BL/6J (B6) and nonresponsive DBA/2J (D2) mice demonstrated that HCB produced a large increase in P3-450 and a very small increase in P1-450 in the responsive strain. The increase in P1-450 was not observed after HCB administration to nonresponsive mice, but a small increase in P3-450 was noted. These findings suggested that HCB may act through the Ah receptor. However, HCB was at best a very weak competitor for specific binding of [3H]-TCDD to the putative receptor in rat or mouse hepatic cytosol in vitro, producing decreases in binding of [3H]-TCDD only at very high concentrations (10(-6) to 10(-5) M).

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“…HCB has been reported to be a "mixed-type" inducer in rats (Goldstein et al, 1982;Stonard, 1975;Vizethum et al, 1980),-that is, induction following HCB treatment is similar to that seen with a combination of both 3-methylcholanthrene (3-MC) or benzo[a] pyrene and PB. In Japanese quail, the overall pattern of induction that occurred with HCB was consistent with a "mixed-type" induction, with effects on the cytochrome P-450 system quite distinct from those seen with either PB or BNF (Table 5).…”

Section: Discussionmentioning

confidence: 90%

A comparison of the effects of hexachlorobenzene, β‐naphthoflavone, and phenobarbital on cytochrome p‐450 and mixed‐function oxidases in Japanese quail

Carpenter

Williams

Buhler

1985

Journal of Toxicology and Environmental Health

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Hexachlorobenzene (HCB), beta-naphthoflavone (BNF), or phenobarbital (PB) was administered to Japanese quail to determine their effects on hepatic porphyrin levels and drug-metabolizing enzymes. While HCB increased porphyrin levels, PB slightly reduced them, and BNF had no effect. HCB was an excellent inducer in quail, increasing the specific content of cytochrome P-450 to levels similar to those produced by BNF. Additional similarities between HCB- and BNF-treated quail included a comparable hypsochromic absorption shift in the CO-reduced difference spectra of cytochrome P-450 and similar effects on the activities of cytosolic glutathione S-transferase (GSH-t), biphenyl hydroxylase (BPH), and ethoxyresorufin O-deethylase (EROD). However, a differential response to HCB and BNF treatment was seen in the activities of hepatic NADPH-cytochrome P-450 reductase, epoxide hydrolase, GSH-t (microsomal), aryl hydrocarbon hydroxylase (AHH), and ethoxycoumarin O-deethylase (ECOD). The activities of NADPH-cytochrome P-450 reductase, AHH, and ECOD following treatment with HCB were similar to those found after dosing with PB. HCB caused a pattern of induction that was distinct from either BNF or PB and appeared to be a "mixed-type" inducer. The rapidity of the HCB-induced porphyrogenic response of Japanese quail, as compared to mammals, may provide unique advantages for making correlations between the in vivo metabolism of haloaromatic hydrocarbons and their effects on porphyrin metabolism.

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Enzymic and electrophoretic characterization of the hexachlorobenzene-induced cytochrome P-450 in the liver of rat

Cited by 18 publications

References 29 publications

Induction of Liver Microsomal Cytochrome P‐450 and Associated Monooxygenases by Octachlorostyrene in the Rat

Induction of Liver Microsomal Cytochrome P‐450 and Associated Monooxygenases by Octachlorostyrene in the Rat

Induction of cytochrome P‐450 isozymes by hexachlorobenzene in rats and aromatic hydrocarbon (Ah)—Responsive mice

A comparison of the effects of hexachlorobenzene, β‐naphthoflavone, and phenobarbital on cytochrome p‐450 and mixed‐function oxidases in Japanese quail

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