Disease relevance of AROCLOR 1254

• The liquid residue from ethereal extracts produced a dose-dependent increase of mutants in Salmonella typhimurium TA98 and TA100 strains; mutagenicity required the presence of a fortified liver microsomal activation system induced by Aroclor 1254 in adult male BD VI inbred rats [1].
• At the end of the year, 26 of 37 (70.3%) trout fed 6 ppb AFB1 had hepatocellular carcinomas, compared to 14 of 46 (30.4%) trout fed 6 ppb AFB1 plus 100 ppm Aroclor 1254, a highly significant reduction in tumor incidence in the trout on the Aroclor 1254-containing diet [2].
• Glycogen depletion of hepatocytes and hyperemia, and white pulp depletion of the spleen were the only changes induced by Aroclor 1254 [2].
• Antitumor activity of a polychlorinated biphenyl mixture, Aroclor 1254, in rats inoculated with Walker 256 carcinosarcoma cells [3].
• In parallel experiments, the effects of pretreatment with PB, Aroclor 1254, pregnenolone-16 alpha-carbonitrile, butylated hydroxytoluene, beta-naphthoflavone, and ethanol on DMN-induced alkylation of liver DNA were studied at a DMN dose of 5 micrograms/kg body weight [4].

Psychiatry related information on AROCLOR 1254

• Horizontal motor activity was significantly lower in rats dosed with 30 mg/kg Aroclor 1254 [5].
• Importantly, Aroclor 1254 caused permanent auditory deficits (20-30 dB threshold shift) at the lowest frequency tested (1 kHz) in both the 4 and 8 mg/kg groups, whereas auditory thresholds were not significantly affected at higher frequencies (4, 16, 32, or 40 kHz) [6].
• Spatial reversal learning in Aroclor 1254-exposed rats: sex-specific deficits in associative ability and inhibitory control [7].
• The present findings demonstrated that the critical period for the ototoxicity of developmental A1254 exposure is within the first few postnatal weeks in the rat [8].
• Adult male and female offspring of female rats fed Aroclor 1254 (Lot #124-191; doses of 0, 1, or 6 mg/kg/day; gestational day 6 through postnatal day 21; n = eight/group) were trained to perform a signal detection task capable of assessing sensory thresholds [9].

High impact information on AROCLOR 1254

• To further enhance the applicability of this new replating system, an exogenous source of metabolic activation was added: a 9,000 X g supernatant from Aroclor 1254-induced rat hepatic S-9 [10].
• A mixture of polychlorinated biphenyls (PCB), Aroclor 1254, was administered ip (500 mg/kg) to pregnant Swiss noninbred CD-1 mice on the 19th day of gestation [11].
• Intact and homogenized hepatocytes from untreated or Aroclor 1254-treated male and female noninbred Sprague-Dawley rats and noninbred Syrian golden hamsters were compared for their ability to metabolize chemicals in the Salmonella-mammalian microsome mutagenesis assay [12].
• Duplicate lots of 120 rainbow trout (Salmo gairdneri) fingerlings were fed for 1 year semipurified diets containing 6 ppb aflatoxin B1 (AFB1), 100 ppm Aroclor 1254 (a polychlorinated biphenyl), and 6 ppb AFB1 plus 100 ppm Aroclor 1254 [2].
• Studies with [14C]aminopyrine, a cytochrome P-450 substrate, showed that TCDD and 3MC had no effect on 14CO2 half-life or aminopyrine N-demethylase; Aroclor 1254 and phenobarbital decreased 14CO2 half-life and stimulated aminopyrine N-demethylase [13].

Chemical compound and disease context of AROCLOR 1254

• The prophage lambda cIts857 induction test with Escherichia coli K12 envA uvrB as the lysogen has been successfully applied to the screening of sparingly water-soluble carcinogens that have been dissolved in dimethyl sulfoxide and metabolically activated with liver enzymes induced either with Aroclor 1254 or phenobarbital [14].
• Mechanisms governing the effect of polychlorinated biphenyl (PCB) toxicity on hypothalamic serotonergic function and the neuroendocrine system controlling LH secretion were investigated in Atlantic croaker (Micropogonias unulatus) exposed to the PCB mixture Aroclor 1254 (1 microg x g body weight(-1) x day(-1)) in the diet for 30 days [15].
• Adenine together with certain 9-N-substituted derivatives such as 9-methyl, 9-benzyl, 9-benzhydryl, and 9-trityl were tested against Salmonella typhimurium strains TA97, TA98, and TA100 in the absence and presence of rat hepatic S9 prepared from Aroclor 1254 pretreated rats [16].
• The highest dose of Aroclor 1242 and both doses of Aroclor 1254 decreased adult body weight, while other treatments did not [17].
• Thyroxine replacement attenuates hypothyroxinemia, hearing loss, and motor deficits following developmental exposure to Aroclor 1254 in rats [18].

Biological context of AROCLOR 1254

• Treatment of pregnant mice with a mixture of polychlorinated biphenyls (PCB's), 500 mg Aroclor 1254/kg, on the last day of gestation caused a large elevation in DMN demethylase activity in the livers of their sucklings, relative to the normal ontogenic increase, reaching a maximum at postnatal day 21 [19].
• To investigate the hypothesis that tumor promotion by chlorinated aromatic hydrocarbons involves Ah receptor occupation and subsequent induction of cytochromes P-450 1a-1, effects of Aroclor 1254 or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were examined in N-nitrosodiethylamine-initiated mice with different Ah receptor phenotype [20].
• When Aroclor 1254 and iron were administered together there was a synergistic increase in the mononucleated diploid fraction which was significant at 2 weeks and highly significant at 6 months [21].
• Induction of nuclear transcription factors, cytochrome P450 monooxygenases, and glutathione S-transferase alpha gene expression in Aroclor 1254-treated rat hepatocyte cultures [22].
• Two PCBs, 2,3,3',4,4',5- and 2,2',3,4,4',5-hexachlorobiphenyl, which resembled Aroclor 1254 in their mode of monooxygenase enzyme induction, also elevated hepatic receptor protein levels but were less active than the PB-type inducers [23].

Anatomical context of AROCLOR 1254

• Results were similar with the rat preparations, except that only large quantities of Aroclor 1254-treated intact male rat hepatocytes appeared to activate DENA [12].
• BP and 2-HOBP were tested for mutagenicity towards two strains of Salmonella typhimurium and towards Chinese hamster V79 cells in the presence of hepatic microsomes from rats pretreated with Aroclor 1254 [24].
• The cytotoxicity of N,N',N''-triethylenethiophosphoramide (thiotepa) was studied in vitro in the MCF-7 human breast carcinoma cell line and in vivo using the EMT6 mouse mammary tumor model, under various conditions of oxygenation and in the presence and absence of Aroclor 1254-induced liver preparations [25].
• Ingestion of diets containing Aroclor 1254, a mixture of polychlorinated biphenyls, for 2 years led to a dose-related increase in the incidence of focal lesions in the glandular stomachs of male and female F344 rats [26].
• Incubation of the carcinogenic polycyclic aromatic hydrocarbon dibenz[a,h]anthracene (DBA) with liver microsomes of Sprague-Dawley rats, pretreated with Aroclor 1254, yielded more than 30 metabolites [27].

Associations of AROCLOR 1254 with other chemical compounds

• Expression of mutagenic activity was dependent on both pretreatment of the rats with Aroclor 1254 and addition of NADPH; unmetabolized steviol was not active [28].
• The increases in epoxide hydratase activities produced by BHA were far greater (11-fold) than were those produced by the administration of well-known enzyme inducers such as 3-methylcholanthrene, phenobarbital, and Aroclor 1254 (2- to 3-fold) [29].
• Isosafrole induces cytochrome P-450d to a greater extent than cytochrome P-450c, Aroclor 1254 induces both hemoproteins to similar extents, and the remaining four compounds preferentially induce cytochrome P-450c relative to cytochrome P-450d [30].
• The most effective metabolism of 11-CH3-CPP-17-one occurred in the presence of Aroclor 1254-induced microsomes, the principal metabolites being oxidative products of the A- and D-rings and of the methyl substituent [31].
• Male Swiss mice were given NDMA on postnatal day 4 and Aroclor 1254 (250 mg/kg) on day 8, and killed at intervals [32].
• Taken together, these findings show a detrimental effect of Aroclor 1254 on rat prostate cells and indicate a possible association between exposure to polychlorinated biphenyl mixture and induction of transformation process in prostate cells [33].

Gene context of AROCLOR 1254

• Levels and membrane localization of the c-K-ras p21 protein in lungs of mice of different genetic strains and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor 1254 [34].
• These tests were also used to demonstrate that dimethyl nitrosamine (DMNA) is activated by Aroclor-1254-induced rat-liver S9 fractions to genotoxic products, as measured by the low survival of a recA derivative compared with the repair-proficient wild-type strain [35].
• Aroclor 1254-induced and uninduced rat liver microsomes were compared to human liver microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms [36].
• 4. Similarly, c/EBP transcripts were only detected in treated cell cultures, but MRP1, its isoforms 3-5 as well as MDR-1 were increased threefold after dosing with Aroclor 1254 [37].
• Brain accumulation of the main PCB congeners after prenatal exposure to Aroclor 1254 and its influence on hypothalamic expression of AhR/ARNT was also assessed [38].

Analytical, diagnostic and therapeutic context of AROCLOR 1254

• In Northern-blot analysis a probe specific to gene 4 (which is designated now as CYP2B12) hybridized to a single mRNA present in the preputial gland, an organ which is used as a model for sebaceous glands, but did not hybridize to mRNA isolated from the liver or from five other tissues of untreated or Aroclor 1254-treated rats [39].
• Mice were given phenobarbital (PB), Aroclor 1254, beta-naphthoflavone (BNF) or corn oil, i.p., followed 3-5 days later with oral administration of MeIQx [40].
• In addition, rats were pretreated with Aroclor 1254 (PCB), 3-methylcholanthrene (MC), phenobarbital (PB), PhIP and corn oil prior to a single dose of [14C]PhIP, and compared with a control group receiving [14C]PhIP only [41].
• After treatment with aroclor-1254, phenobarbital or 3-methylcholanthrene total cytochrome P450 was 1.7-2.7 times induced [42].
• Centrilobular hepatocyte hypertrophy occurred consistently in mice given intraperitoneal injections of the polychlorinated biphenyl (PCB) mixture Aroclor 1254 [43].

References