Disease relevance of HCB

• Patients whose hepatitis C (HCV) and hepatitis B (HBV) serostatus was known were classified as being infected by HCV alone, HBV alone (HBsAg positive), both HCV and HBV, or neither HCB nor HBV [1].
• Thus the considerable sensitisation of the C57BL/10 strain after iron overload to the induction of porphyria by HCB cannot be ascribed simply to enhancement of total metabolism but must be caused either by the formation of a specific undetected metabolite or induction of some other toxic process [2].
• Liver toxicity is more frequent among subjects with chronic HCV and/or HCB co-infections and alcohol users [3].
• Beneficial substrate interactions included enhanced degradation of benzene and p-xylene by the presence of toluene in Pseudomonas sp. strain CFS-215 incubations, as well as benzene-dependent degradation of toluene and p-xylene by Arthrobacter sp. strain HCB [4].
• Pregnant mice were treated with TCDD and either HCB on gestation Days 10 through 13, and the fetuses examined for the presence of cleft palate and renal abnormalities on gestation Day 18 [5].

High impact information on HCB

• However, anti-P-448HCB inhibited N-hydroxylation by 60% in both 3-MC- and HCB-induced microsomes [6].
• These results show the hepatic TCDD-binding protein(s) induced upon pretreatment of Sprague-Dawley rats with TCDD/HCB to be kinetically distinct from the Ah receptor, but structurally very similar [7].
• Glycosylation of the HCB 4,6-O-cyclohexylidenemannoside 5 with primary alcohols was also highly beta-selective, and the HCB 2,3-O-cyclohexylidenemannoside 6 exhibited the moderate beta-selectivity [8].
• Moreover, P-450 3-dependent steroid 7 alpha-hydroxylase activity was not detected in these extrahepatic tissues of control or HCB-treated rats (less than or equal to 1% of that found in the corresponding liver microsomes of untreated or HCB-treated rats) [9].
• Since the identification of inducers with such unique characteristics would have implications with regard to the mechanism of induction of all four isozymes, we have examined the induction of cytochromes P-450b and P-450e by HCB and cytochromes P-450c and P-450d by 3-MeO-AAB in liver microsomes from adult male rats [10].

Chemical compound and disease context of HCB

• PURPOSE: To evaluate the associations of serum levels of p,pacute;-DDE and two other persistent organochlorine pesticides, beta-HCH and HCB, in relation to preterm birth [11].
• Pretreatment of these animals with 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) or 3,4,3',4'-tetrachlorobiphenyl (TCB) protected against benzene toxicity for as long as 7 days, but not after 10 days of repeated dosing [12].
• This study shows that thyroid hormone plays an important role in the early establishment of HCB induced porphyria [13].
• For this purpose, a time-course study (2, 3 and 4 weeks of hexachlorobenzene treatment) of phospholipid pattern and porphyrin content was performed comparatively in two strains of rats (Wistar and Chbb THOM) which differ in their susceptibility to develop HCB-induced porphyria [14].

Biological context of HCB

• In these animals the tissue accumulation of HCB and enzyme induction resembled the situation in C57 mice fed ad libitum [15].
• C57BL/6J (C57) and DBA/JBOMf (DBA) mice were used to study the role of adipose tissue as a modifier of tissue distribution, biological effects, and elimination of a lipophilic foreign chemical, 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) [15].
• HCB was compared with HBB and FF-1 for cell growth toxicity at 37 and 75 microgram/ml [16].
• Data are compatible with describing the kinetics of HCB by a two-compartment open model, where elimination occurs from a part of the peripheral compartment [17].
• Some compounds, such as transnonachlor and HCB, had similar rates of increase throughout the food web, whereas compounds that are more readily eliminated (gamma-HCH) showed no relationship with trophic level [18].

Anatomical context of HCB

• The adipose tissue content also affected the rate of elimination of HCB [15].
• Although cytochrome P-448HCB is the predominant cytochrome in liver microsomes from HCB-induced rats, the magnitude of the induction of this isozyme (40-fold) is lower than that of P-448MC (600-fold), because cytochrome P-448HCB is present in higher concentrations in livers of untreated rats than P-448MC (90 versus 3 pmol/mg) [19].
• In addition, a study on the influence of the chronic exposure to two polyhalogenated hydrocarbons, PCB and HCB, on several parameters of lymphocyte function in mice is presented [20].
• These results indicate that the effects of HCB on serum testosterone levels reflect its effects on testicular function rather than the pituitary or hypothalamus [21].
• The significance of the levels of the fungicide HCB in breast milk cannot be determined [22].

Associations of HCB with other chemical compounds

• Anti-P-448MC inhibited AAF metabolism approximately 43% in microsomes from 3-MC-induced male rats and 30% in microsomes from rats treated with 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), another 3-MC-type inducer [6].
• The latent BCB-disaccharide 23, which was obtained from the HCB mannoside 4 as the donor and the BCB glucoside 12 as the acceptor by the present glycosylation method, was converted into the active HCB-disaccharide 39 by selective hydrogenolysis [8].
• In order to study the lactational transfer of polychlorinated biphenyls, lactating rats were treated with a low dose of either 3,4,3',4'-tetrachlorobiphenyl (TCB), 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) or a combination of TCB and HCB [23].
• Lactational transfer of either TCB or HCB reduced marginally peroxisomal enzyme activities; however, exposure to a combination of TCB and HCB resulted in the highly significant reduction in KCN-insensitive palmitoyl-CoA oxidation and acetyl-CoA oxidation [24].
• The PB-like inducers, 2,2',4,4',5, 5'-hexachlorobiphenyl (HCB) and 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethane (o,p-DDD), proportionally induced the CYP2B1/2B2 and UDPGT genes and activated the plasmid (HCB = PB > DDD) [25].

Gene context of HCB

• We propose that embryotoxicity and retarded embryo growth result from impairment of PR function and that differences in the efficacy of HCB treatments are a result of their dose-dependent, partial estrogenic actions which increase PR Rt via up-regulation of ER [26].
• As in the human syndrome porphyria cutanea tarda, iron administration increased porphyrin accumulation and the degree of reduction of UROD activity in mice fed HCB [27].
• Furthermore, animals exposed to HCB and dieldrin, but not to PCB, had a profound decrease in their resistance to a challenge tumor cell implant which was related to a select alteration in tumor cell killing [28].
• Treatment with HCB did not increase neonatal ethoxyresorufin-O-de-ethylation (EROD) activities whereas a more than 26-fold increase in EROD activity was noted in response to exposure to TCB [24].
• Analysis of HCB and BHC isomer residues in food [29].

Analytical, diagnostic and therapeutic context of HCB

• P-450 3 was not detected on Western blots of lung, kidney, or prostate microsomes isolated from control or HCB-treated rats (less than or equal to 2% of that found in livers of HCB-treated rats) [9].
• Urinary HCB excretion over the next 24 hr, measured by gas chromatography, was 10-fold greater in the group treated with anti-HCB Fab (P < 0.01) [30].
• The results show a statistically significant decrease in the placental blood flow and an increase in the pulmonary blood flow in the animals fed with 30 mg HCB compared to the control groups [31].
• Quantitative and qualitative microsocopic fluorescence analysis showed that the cytoplasmic inclusions are formed as early as 3 hr after treatment with HCB [32].
• Particularly, POPs analytical methods were established using native and (13)C-labeled internal standards of HCHs, HCB, cyclodienes, chlordanes, DDTs, mirex, dioxin-like PCBs, PCDDs, and PCDFs by isotope dilution technique [33].

References