Disease relevance of HEXACHLOROBENZENE

• These findings suggest that lipid peroxidation and mitochondrial dysfunction may contribute to the hepatotoxicity seen in hexachlorobenzene-induced porphyria [1].
• Evidence for an environmental predisposition was less clear cut, but it is interesting that members of both families used a gamma isomer of hexachlorobenzene (Nickoff) to eradicate mite infestations in their birds which might have damaged the bronchial mucosa or acted as an immunologic adjuvant in a person with underlying susceptibility to disease [2].
• These studies demonstrate that not only are female rats far more sensitive than males to the porphyrinogenic effects of HCB but also to the hepatocarcinogenic actions, suggesting a link between these two manifestations of toxicity that may also apply to other polyhalogenated aromatics [3].
• Pre-loading of C57BL/10ScSn mice with iron greatly sensitizes them to the induction of hepatic porphyria caused by hexachlorobenzene (HCB) (Smith and Francis, 1983) [4].
• Under the influence of iron overload EROD was significantly depressed from HCB alone, but not the others or cytochrome P450 reductase [5].

Psychiatry related information on HEXACHLOROBENZENE

• Behaviors evaluated in pups exposed maternally to HCB included the negative geotaxic reflex on postnatal day (PND) 6, 8, and 10, olfactory discrimination (PND 9-11), and the development of exploratory behavior (PND 15-20) [6].
• Effect of food deprivation on low level hexachlorobenzene exposure in rats [7].
• The effect of reaction time on HCB dechlorination and the pathway of dechlorination were investigated using the Ca-Fe composite oxide with the highest activity [8].
• The levels of p,p'-DDT, p,p'-DDE, dieldrin, alpha- and beta-hexachlorocyclohexane (alpha-HCH, beta-HCH), hexachlorobenzene and polychlorinated biphenyls (PCBs) were determined in milk fat from mothers with different dietary habits [9].

High impact information on HEXACHLOROBENZENE

• In an antibody-dependent cell-mediated cytotoxicity test using isolated hepatocytes from normal and hexachlorobenzene-treated (porphyric) rats as targets, it was found that sera from group 1a produced high cytotoxicity against porphyric hepatocytes and low or zero cytotoxicity against normal hepatocytes (p less than 0.001) [10].
• HCB treatments resulted in increased proliferation of normal hepatocytes, which was not observed for PECB under the same treatment regimen [11].
• The best description of the data resulted from the model incorporating the hypothesis that PECB and HCB promoted the growth of foci via increased net growth rates of B cells [11].
• There was a significant increase in mitochondrial lipid peroxidation in rats treated with hexachlorobenzene alone and hexachlorobenzene + Fe [1].
• Hexachlorobenzene, benzo(a)pyrene, and beta-naphthoflavone were effective AHR agonists in the yeast system, and had EC50 values of 200, 40, and 20 nM, respectively, for beta-galactosidase activity induction [12].

Chemical compound and disease context of HEXACHLOROBENZENE

• Continuous administration of ALA markedly accelerates the onset of porphyria in iron-loaded male C57BL/6 mice after a single intraperitoneal dose of hexachlorobenzene (200 mg/kg); mice given phenobarbitone and ALA do not become porphyric [13].
• Bile and biliary lipid secretion in rats with hexachlorobenzene-induced porphyria. Effect of S-adenosyl-L-methionine administration [14].
• Search for Ha-ras codon 61 mutations in liver tumours caused by hexachlorobenzene and Aroclor 1254 in C57BL/10ScSn mice with iron overload [15].
• During the second follow-up period, the risk of otitis media increased with prenatal exposure to p,p'-DDE, hexachlorobenzene, and dieldrin [16].
• The role of pentachlorophenol in causing mitochondrial derangement in hexachlorobenzene induced experimental porphyria [17].

Biological context of HEXACHLOROBENZENE

• Current lactation specimens of porphyric patients show high HCB levels, up to 3.12 ppm, but the infant offspring appear normal [18].
• The sex difference in tumour response could not be explained by differences in hepatic HCB concentrations [3].
• As ME gene expression is regulated mainly by thyroid hormones, we next investigated the role of T3 receptor (T3R) in the ME gene transcriptional induction mediated by HCB [19].
• Epidemiology of hexachlorobenzene-induced porphyria in Turkey: clinical and laboratory follow-up after 25 years [18].
• Most humans have detectable body burdens of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and p,p'-dichlorophenyldichloroethylene p,p'-DDE), a metabolite of p,p'-dichlorodiphenyltrichloroethane (DDT) [20].

Anatomical context of HEXACHLOROBENZENE

• For example, an increase in erythrocyte protoporphyrin is a useful measurement for early detection of exposure to lead and porphyrinuria was an early manifestation of a hexachlorobenzene-induced porphyria in Turkey [21].
• There was no major difference in the ability to hydroxylate HCB between hepatic microsomes from induced C57BL/10 mice and those from the insensitive DBA/2 strain [22].
• Hexachlorobenzene treatment, therefore, does not affect the iron status of the mitochondria [23].
• Hexachlorobenzene (HCB) elicits concentration-dependent and saturable type 1 binding spectra when added to oxidized (Fe3+) cytochrome P-450 (CYT P-450) in control, phenobarbital- (PB) induced, and beta-naphthoflavone- (BNF) induced male Sprague-Dawley rat liver microsomes [24].
• 2. Hexachlorobenzene has no effect on erythrocyte porphyrin content, but produces a decrease in that of Harderian gland and an increase in the porphyrin content of the kidney and spleen, and a marked increase in the liver (1 mumol/g of tissue) [25].

Associations of HEXACHLOROBENZENE with other chemical compounds

• Analytes included common PCB congeners, the DDT metabolites p,p'-DDE, and o,p'-DDE as well as the pesticides: hexachlorobenzene (HCB); and the three isomers of hexachlorocyclohexane (alpha,beta and gamma-HCH) [26].
• Hexachlorobenzene (HCB) is a dioxin-type chemical that acts mainly through the aryl hydrocarbon receptor [19].
• This effect is specific for ME, as other liver enzymes, such as glyceraldehyde-3-phosphate dehydrogenase, phosphoenol pyruvate carboxykinase, and mitochondrial alpha-glycerol-3-phosphate dehydrogenase, are not affected by HCB [19].
• By contrast, lipid peroxidation, in the presence of NADPH, was 8-fold greater in control C57BL/10 microsomes than in DBA/2 microsomes and was stimulated by iron treatment (although not by HCB) [22].
• They include the pesticides aldrin, chlordane, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, mirex, and toxaphene [27].

Gene context of HEXACHLOROBENZENE

• The role of the Ah locus in hexachlorobenzene (HCB)-induced porphyria and the possible involvement of P-450 cytochromes P(1)450 and P(3)450 in the pathogenesis of this disease were investigated in two congenic strains of C57BL/6J mice that differ only at this locus [28].
• The IRS-1 phosphorylation increased in HCB rats; however, it decreased in NMU-HCB vs. NMU [29].
• IR, IGF-IR, and IRS-1 levels were higher in HCB than in controls [29].
• In HCB exposed Lewis rats and T. spiralis infected BN rats the IL-4 mRNA expression correlated with IgE levels and T. spiralis infection, respectively, whereas the IL-4 production lacked correlation in all cases [30].
• Hexachlorobenzene reduced the levels of IL-5, IL-10 and IFN-gamma [31].

Analytical, diagnostic and therapeutic context of HEXACHLOROBENZENE

• A clonal growth model: time-course simulations of liver foci growth following penta- or hexachlorobenzene treatment in a medium-term bioassay [11].
• Thus mitochondrial preparations, which were further depleted of lysosomes by Percoll-density-gradient centrifugation, contained 2.78 +/- 0.75 and 2.99 +/- 0.49 nmol of non-haem iron/mg of protein when isolated from the liver of control rats and hexachlorobenzene-treated rats respectively [23].
• These descriptive findings are in agreement with previously reported associations between soft-tissue sarcoma and human exposure to organochlorinated compounds, as well as with animal experiments relating HCB and thyroid cancer, and add new information on the possible relation between organochlorinated compounds, and particularly HCB, and cancer [32].
• Serum HCB was analyzed by gas chromatography coupled with electron capture detection [33].
• No significant difference in mean breast adipose tissue levels of HCB was observed between breast cancer patients (21.0 ppb) and controls (19.1 ppb) in this large case-control study [34].

References