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Chemical Compound Review

AROCLOR 1254     1,2,3-trichloro-4-(2,3- dichlorophenyl)benzene

Synonyms: Aroclor1254, Arochlor 1254, Arclor1254, CCRIS 900, SureCN811508, ...
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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


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


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


  1. Mutagenicity of extracts of pickled vegetables collected in Linhsien County, a high-incidence area for esophageal cancer in Northern China. Lu, S.H., Camus, A.M., Tomatis, L., Bartsch, H. J. Natl. Cancer Inst. (1981) [Pubmed]
  2. Inhibitory effect of a polychlorinated biphenyl (Aroclor 1254) on aflatoxin B1 carcinogenesis in rainbow trout (Salmo gairdneri). Hendricks, J.D., Putnam, T.P., Bills, D.D., Sinnhuber, R.O. J. Natl. Cancer Inst. (1977) [Pubmed]
  3. Antitumor activity of a polychlorinated biphenyl mixture, Aroclor 1254, in rats inoculated with Walker 256 carcinosarcoma cells. Kerkvliet, N.I., Kimeldorf, D.J. J. Natl. Cancer Inst. (1977) [Pubmed]
  4. Effect of phenobarbital and other liver monooxygenase modifiers on dimethylnitrosamine-induced alkylation of rat liver macromolecules. Schwarz, M., Buchmann, A., Klormann, H., Schrenk, D., Kunz, W. Cancer Res. (1985) [Pubmed]
  5. Repeated exposure of adult rats to Aroclor 1254 causes brain region-specific changes in intracellular Ca2+ buffering and protein kinase C activity in the absence of changes in tyrosine hydroxylase. Kodavanti, P.R., Derr-Yellin, E.C., Mundy, W.R., Shafer, T.J., Herr, D.W., Barone, S., Choksi, N.Y., MacPhail, R.C., Tilson, H.A. Toxicol. Appl. Pharmacol. (1998) [Pubmed]
  6. Developmental exposure to polychlorinated biphenyls (Aroclor 1254) reduces circulating thyroid hormone concentrations and causes hearing deficits in rats. Goldey, E.S., Kehn, L.S., Lau, C., Rehnberg, G.L., Crofton, K.M. Toxicol. Appl. Pharmacol. (1995) [Pubmed]
  7. Spatial reversal learning in Aroclor 1254-exposed rats: sex-specific deficits in associative ability and inhibitory control. Widholm, J.J., Clarkson, G.B., Strupp, B.J., Crofton, K.M., Seegal, R.F., Schantz, S.L. Toxicol. Appl. Pharmacol. (2001) [Pubmed]
  8. PCBs, thyroid hormones, and ototoxicity in rats: cross-fostering experiments demonstrate the impact of postnatal lactation exposure. Crofton, K.M., Kodavanti, P.R., Derr-Yellin, E.C., Casey, A.C., Kehn, L.S. Toxicol. Sci. (2000) [Pubmed]
  9. Gender-dependent behavioral and sensory effects of a commercial mixture of polychlorinated biphenyls (Aroclor 1254) in rats. Geller, A.M., Oshiro, W.M., Haykal-Coates, N., Kodavanti, P.R., Bushnell, P.J. Toxicol. Sci. (2001) [Pubmed]
  10. A method for the amplification of chemically induced transformation in C3H/10T1/2 clone 8 cells: its use as a potential screening assay. Schechtman, L.M., Kiss, E., McCarvill, J., Nims, R., Kouri, R.E., Lubet, R.A. J. Natl. Cancer Inst. (1987) [Pubmed]
  11. Effects of polychlorinated biphenyls on lung and liver tumors initiated in suckling mice by N-nitrosodimethylamine. Anderson, L.M., van Havere, K., Budinger, J.M. J. Natl. Cancer Inst. (1983) [Pubmed]
  12. Metabolic activation by hamster and rat hepatocytes in the Salmonella mutagenicity assay. Poiley, J.A., Raineri, R., Andrews, A.W., Cavanaugh, D.M., Pienta, R.J. J. Natl. Cancer Inst. (1980) [Pubmed]
  13. Detection of carcinogen-induced stimulation of cytochrome P-448-associated enzymes by 14CO2 breath analysis studies using dimethylaminoazobenzene. Hepner, G.W., Piken, E.P. Gastroenterology (1979) [Pubmed]
  14. Screening of carcinogens with the prophage lambda cIts857 induction test. Ho, Y.L., Ho, S.K. Cancer Res. (1981) [Pubmed]
  15. Disruption of neuroendocrine control of luteinizing hormone secretion by aroclor 1254 involves inhibition of hypothalamic tryptophan hydroxylase activity. Khan, I.A., Thomas, P. Biol. Reprod. (2001) [Pubmed]
  16. Mutagenicity testing of 9-N-substituted adenines and their N-oxidation products. Gorrod, J.W., Ioannides, C., Lam, S.P., Neville, S. Environ. Health Perspect. (1993) [Pubmed]
  17. Neonatal polychlorinated biphenyl treatment increases adult testis size and sperm production in the rat. Cooke, P.S., Zhao, Y.D., Hansen, L.G. Toxicol. Appl. Pharmacol. (1996) [Pubmed]
  18. Thyroxine replacement attenuates hypothyroxinemia, hearing loss, and motor deficits following developmental exposure to Aroclor 1254 in rats. Goldey, E.S., Crofton, K.M. Toxicol. Sci. (1998) [Pubmed]
  19. Dimethylnitrosamine demethylase activity in fetal, suckling, and maternal mouse liver and its transplacental and transmammary induction by polychlorinated biphenyls. Jannetti, R.A., Anderson, L.M. J. Natl. Cancer Inst. (1981) [Pubmed]
  20. Promotion of N-nitrosodiethylamine-initiated hepatocellular tumors and hepatoblastomas by 2,3,7,8-tetrachlorodibenzo-p-dioxin or Aroclor 1254 in C57BL/6, DBA/2, and B6D2F1 mice. Beebe, L.E., Fornwald, L.W., Diwan, B.A., Anver, M.R., Anderson, L.M. Cancer Res. (1995) [Pubmed]
  21. Perturbation of hepatocyte nuclear populations induced by iron and polychlorinated biphenyls in C57BL/10ScSn mice during carcinogenesis. Madra, S., Styles, J., Smith, A.G. Carcinogenesis (1995) [Pubmed]
  22. Induction of nuclear transcription factors, cytochrome P450 monooxygenases, and glutathione S-transferase alpha gene expression in Aroclor 1254-treated rat hepatocyte cultures. Borlak, J., Thum, T. Biochem. Pharmacol. (2001) [Pubmed]
  23. Elevation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) polychlorinated biphenyls. Structure-activity relationships. Denomme, M.A., Leece, B., Li, A., Towner, R., Safe, S. Biochem. Pharmacol. (1986) [Pubmed]
  24. Carcinogenicity of 2-hydroxybenzo(a)pyrene and 6-hydroxybenzo(a)pyrene in newborn mice. Chang, R.L., Wislocki, P.G., Kapitulnik, J., Wood, A.W., Levin, W., Yagi, H., Mah, H.D., Jerina, D.M., Conney, A.H. Cancer Res. (1979) [Pubmed]
  25. Evidence for enzymatic activation and oxygen involvement in cytotoxicity and antitumor activity of N,N',N''-triethylenethiophosphoramide. Teicher, B.A., Waxman, D.J., Holden, S.A., Wang, Y.Y., Clarke, L., Alvarez Sotomayor, E., Jones, S.M., Frei, E. Cancer Res. (1989) [Pubmed]
  26. Aroclor 1254-induced intestinal metaplasia and adenocarcinoma in the glandular stomach of F344 rats. Morgan, R.W., Ward, J.M., Hartman, P.E. Cancer Res. (1981) [Pubmed]
  27. Regio- and stereoselective metabolism of dibenz[a,h]anthracene: identification of 12 new microsomal metabolites. Platt, K.L., Reischmann, I. Mol. Pharmacol. (1987) [Pubmed]
  28. Metabolically activated steviol, the aglycone of stevioside, is mutagenic. Pezzuto, J.M., Compadre, C.M., Swanson, S.M., Nanayakkara, D., Kinghorn, A.D. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  29. Enhancement of liver microsome epoxide hydratase activity in rodents by treatment with 2(3)-tert-butyl-4-hydroxyanisole. Cha, Y.N., Martz, F., Bueding, E. Cancer Res. (1978) [Pubmed]
  30. Induction of two immunochemically related rat liver cytochrome P-450 isozymes, cytochromes P-450c and P-450d, by structurally diverse xenobiotics. Thomas, P.E., Reik, L.M., Ryan, D.E., Levin, W. J. Biol. Chem. (1983) [Pubmed]
  31. Cytochrome P450-dependent metabolism and mutagenicity of 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one and their implications in its carcinogenicity. Boyd, G.W., Young, R.J., Harvey, R.G., Coombs, M.M., Ioannides, C. Carcinogenesis (1993) [Pubmed]
  32. Promotion by polychlorinated biphenyls of lung and liver tumors in mice. Anderson, L.M., Logsdon, D., Ruskie, S., Fox, S.D., Issaq, H.J., Kovatch, R.M., Riggs, C.M. Carcinogenesis (1994) [Pubmed]
  33. Aroclor-1254 affects mRNA polyadenylation, translational activation, cell morphology, and DNA integrity of rat primary prostate cells. Cillo, F., de Eguileor, M., Gandolfi, F., Brevini, T.A. Endocr. Relat. Cancer (2007) [Pubmed]
  34. 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. Ramakrishna, G., Anderson, L.M. Carcinogenesis (1998) [Pubmed]
  35. A differential DNA-repair test using mixtures of E. coli K12 strains in liquid suspension and animal-mediated assays. Mohn, G.R., Kerklaan, P.R., ten Bokkum-Coenradi, W.P., ten Hulscher, T.E. Mutat. Res. (1983) [Pubmed]
  36. A comparison of aroclor 1254-induced and uninduced rat liver microsomes to human liver microsomes in phenytoin O-deethylation, coumarin 7-hydroxylation, tolbutamide 4-hydroxylation, S-mephenytoin 4'-hydroxylation, chloroxazone 6-hydroxylation and testosterone 6beta-hydroxylation. Easterbrook, J., Fackett, D., Li, A.P. Chem. Biol. Interact. (2001) [Pubmed]
  37. Expression of drug-metabolizing enzymes, nuclear transcription factors and ABC transporters in Caco-2 cells. Borlak, J., Zwadlo, C. Xenobiotica (2003) [Pubmed]
  38. Ontogenetic development, sexual differentiation, and effects of Aroclor 1254 exposure on expression of the arylhydrocarbon receptor and of the arylhydrocarbon receptor nuclear translocator in the rat hypothalamus. Pravettoni, A., Colciago, A., Negri-Cesi, P., Villa, S., Celotti, F. Reprod. Toxicol. (2005) [Pubmed]
  39. Sequence of a novel cytochrome CYP2B cDNA coding for a protein which is expressed in a sebaceous gland, but not in the liver. Friedberg, T., Grassow, M.A., Bartlomowicz-Oesch, B., Siegert, P., Arand, M., Adesnik, M., Oesch, F. Biochem. J. (1992) [Pubmed]
  40. Role of metabolism on the DNA binding of MeIQx in mice and bacteria. Turteltaub, K.W., Watkins, B.E., Vanderlaan, M., Felton, J.S. Carcinogenesis (1990) [Pubmed]
  41. The effect of dose and enzyme inducers on the metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats. Watkins, B.E., Suzuki, M., Wallin, H., Wakabayashi, K., Alexander, J., Vanderlaan, M., Sugimura, T., Esumi, H. Carcinogenesis (1991) [Pubmed]
  42. Microsomal lauric acid hydroxylase activities after treatment of rats with three classical cytochrome P450 inducers and peroxisome proliferating compounds. Dirven, H.A., van den Broek, P.H., Peters, J.G., Noordhoek, J., Jongeneelen, F.J. Biochem. Pharmacol. (1992) [Pubmed]
  43. Liver scarring induced by polychlorinated biphenyl administration to mice previously treated with diethylnitrosamine. Gans, J.H., Pintauro, S.J. Proc. Soc. Exp. Biol. Med. (1986) [Pubmed]
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