Assessment of the contribution of chlorinated dibenzo-p-dioxins and dibenzofurans to hexachlorobenzene-induced toxicity, porphyria, changes in mixed function oxygenases, and histopathological changes

Goldstein, Joyce A.; Friesen, Marlin D.; Scotti, Thomas M.; Hickman, Patricia; Hass, J. Ronald; Bergman, Hinda

doi:10.1016/0041-008x(78)90309-5

Cited by 50 publications

(14 citation statements)

References 20 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%

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%

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 HCB (> 99% pure), which came from BDH Chemicals Ltd, contained no detectable amounts of chlorinated dibenzo-p-dioxins or dibenzofurans (< 0.5 ppm) (21). Aldrich was the source for 1,3,5-trichlorobenzene (1,3,5-CB) (98% pure), 1,2,4-trichlorobenzene (1,2,4-CB) (99% pure), 1,2,3,4-tetrachlorobenzene (1,2,3,4-CB) (98% pure), and 1,2,3,5-tetrachlorobenzene (1,2,3,5-CB) (99% pure).…”

Section: Methodsmentioning

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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“…Another HCB feeding study noted lung pathology in rats of the same strain. The lung pathology was characterized by hypertrophy and proliferation of endothelial cells lining small pulmonary vessels, perivascular infiltrates of mainly mononuclear cells, and focal accumulations of alveolar macrophages (Goldstein et al 1978). Similar lung lesions, predominantly affecting the lung venules, have been noted in Wistar, Lewis and BN/ Orl Ico rats, although the latter rat strain showed inflammatory infiltrates of mainly eosinophilic granulocytes (Vos et al 1983;Michielsen et al 1997).…”

Section: Introductionmentioning

confidence: 86%

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Michielsen

Zeamari

Leusink-Muis

et al. 2002

Archives of Toxicology

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Based on observations that the persistent environmental pollutant hexachlorobenzene (HCB) induces inflammatory skin lesions and eosinophilic and granulomatous lung pathology as well as in vivo airways hyperresponsiveness to methacholine in the BN/SsNOlaHsd rat (Michielsen et al., Toxicol Appl Pharmacol 172:11-20, 2001), which are features of human Churg-Strauss syndrome (CSS), we have investigated whether HCB induced other features of CSS such as asthma and systemic vasculitis involving the heart and kidneys in this strain of rat. To this end, BN/SsNOlaHsd rats received control feed or feed supplemented with 450 mg/kg HCB. On days 6, 14 or 21, tracheas were isolated to assess non-specific in vitro airways hyperresponsiveness (AHR) to cumulative concentrations of arecoline and serotonin. In addition, lungs were lavaged to count and differentiate lavage cells, and skin, lungs, heart, kidneys, and lymph nodes were processed for histopathological investigation. HCB induced eosinophilic and granulomatous lung pathology in the BN/SsNOlaHsd rat, which became more severe with time and was associated with significant in vitro AHR to arecoline. Moreover, as in CSS-patients, systemic effects on spleen and lymph nodes were observed in HCB-fed BN/SsNOlaHsd rats, as well as development of skin lesions with vascular changes and eosinophilic infiltrates. In contrast, cardiac or renal involvement, frequently seen in CSS-patients, was not seen in HCB-fed rats. More importantly, there were no indications of necrotizing vasculitis, a hallmark feature of CSS, in the lungs and skin of BN/SsNOlaHsd rats. Thus, it is concluded that the persistent environmental pollutant HCB possibly induces a mild or early stage of CSS in the BN/SsNOlaHsd rat that may evolve into fully developed CSS after prolonged exposure to HCB.

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Assessment of the contribution of chlorinated dibenzo-p-dioxins and dibenzofurans to hexachlorobenzene-induced toxicity, porphyria, changes in mixed function oxygenases, and histopathological changes

Cited by 50 publications

References 20 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

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