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At least 19 recordsLinked to original sources
PubMed1979

Comparison of the compositions of Aroclor 1242 and Aroclor 1016.

The complete polychlorinated biphenyl compositions of two American products, Aroclor 1242 and its more modern replacement, Aroclor 1016, have been determined by gas-liquid chromatography (GLC) on twelve liquid phases of differing selectivities. Attempts were made to determine the degree of contamination of these Aroclors with chlorinated naphthalenes, using GLC with multiple ion-monitoring mass spectrometry. Chlorinated dibenzofurans, indetectable in Aroclor 1016, were tentatively identified by negative chemical-ionization mass spectrometry and their retention times relative to dieldrin on two GLC liquid phases. Quantitation of the dibenzofurans was initially accomplished using an electron-capture detector, and confirmed by negative chemical-ionization mass spectrometry. Aroclor 1242 contained less than 0.05 mol.% chloronaphthalenes, while Aroclor 1016 contained less than 0.06 mol.% of these compounds. Aroclor 1242 had approximately 150 ppb of chlorinated dibenzofurans, of which 43% was the toxic 2,3,7,8-tetrachloro isomer.

Aroclors↗
PubMed1987

Induction of the hepatic mixed-function oxidases by Aroclor 1254 in the hamster: comparison of Aroclor-induced rat and hamster preparations in the activation of pre-carcinogens in the Ames test.

Hepatic microsomal mixed-function oxidase activities and the metabolic activation of chemical carcinogens to mutagens in the Ames test were investigated using Aroclor 1254-induced rat and hamster preparations. Benzphetamine N-demethylase, NADPH-cytochrome c reductase and cytochromes P-450 and b5 were induced in both animals to the same extent by pre-treatment with Aroclor. However, the O-deethylation of ethoxyresorufin was markedly induced in the rat (147-fold) but only modestly in the hamster (3-fold). 1,2-Benzanthracene and 4-aminobiphenyl were more efficiently activated by the rat preparations while, in contrast, 2-acetylaminofluorene, 2-aminoanthracene, nitrosopiperidine, nitrosopyrrolidine, cyclophosphamide and phenacetin were more efficiently activated by the hamster preparations. No significant difference was observed in the activation of 3-methylcholanthrene, benzo[a]pyrene and 2-aminofluorene. It is concluded that (a) the hamster is relatively refractive to cytochrome P-448 induction, and (b) Aroclor 1254-induced rat and hamster S9 preparations differ in their ability to convert chemical carcinogens to mutagens in the Ames test.

Animals↗
PubMed1981

Biological activity of technical Aroclor 1254 compared to Aroclor 1254 residues: swine fat residues fed to broiler cockerels.

Fat from Aroclor 1254-treated swine was rendered and incorporated into the diets of broiler chicks for 3-4 weeks. The technical Aroclor 1254 which was fed to the swine was also mixed into control lard for comparison at dietary concentrations of 0.07-9.0 mg/kg. The swine-residue PCB seemed to have a higher proportion of strong microsomal inducers, but the technical PCB was slightly more effective in inducing ethoxy resorufin and p-nitro-anisole (pNA) O-dealkylases than the swine-residue PCB. No overt signs of toxicosis were apparent and none of the diets resulted in changes in growth, relative organ weights, microsomal protein or high affinity pNA O-dealkylase. Increases in cytochrome(s) P-450 were significant only at the higher dietary concentrations (approx. 9 mg/kg) while ethoxyresorufin O-dealkylase was induced at dietary concentrations below 1 mg/kg.

Adipose Tissue↗
PubMed1983

Hepatic microsomal O-de-ethylases in cod (Gadus morhua): their induction by Aroclor 1254 but not by Aroclor 1016.

1. The characteristics of hepatic ethoxycoumarin and ethoxyresorufin O-de-ethylases in juvenile cod (Gadus morhua) from the North Sea are described. 2. Feeding Aroclor 1254 to juvenile cod to produce liver concentrations of approx 900 microgram X g-1 (wet wt) induced ethoxycoumarin O-de-ethylase approx 30-fold, but had no effect on ethoxyresorufin O-deethylase activity. 3. Feeding Aroclor 1016 to juvenile cod to produce liver concentrations of approx 300 micrograms X g-1 (wet wt.) did not induce ethoxycoumarin O-de-ethylase activity.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1981

Promoting effects of polychlorinated biphenyls (Aroclor 1254) and polychlorinated dibenzofuran-free Aroclor 1254 on diethylnitrosamine-induced tumorigenesis in the rat.

The hepatic tumor-promoting activity of a commercial polychlorinated biphenyl mixture, Aroclor 1254 (AR 1254), with and without its intrinsic polychlorinated dibenzofuran (PCDF) impurities, was investigated. Male Sprague-Dawley non-inbred albino rats were treated with 66 microgram diethylnitrosamine (DENA)/ml drinking water for 5 weeks and subsequently given a control diet or a diet supplemented (100 ppm for 18 wk) with either AR 1254 or AR 1254 from which the PCDF moieties were removed (AR 1254-PCDF). Of those animals receiving DENA alone, 16% exhibited hepatocellular carcinomas. Of those rats treated with DENA followed by administration of AR 1254 or AR 1254-PCDF, 64 or 84%, respectively, developed hepatocellular carcinomas. Thus promotion with either AR 1254 or AR 1254-PCDF significantly (P less than 0.05) increased the incidence of DENA-initiated hepatocellular carcinomas. Administration of AR 1254 or AR 1254-PCDF alone did not induce hepatic tumors. Therefore, PCDF impurities were not necessary for the promoting activity of AR 1254.

Animals↗
PubMed1980

Polychlorinated biphenyls (Aroclors 1016 and 1242): effects on survival and reproduction in mink and ferrets.

Diets that contained various levels of supplemental Aroclor 1242 or Aroclor 1016 were fed to mink and ferrets to investigate the chronic toxicity of these PCBs in two closely related species. In mink, Aroclor 1242 was found to be more toxic than comparable or higher levels of Aroclor 1016. The Aroclor 1242 diets caused complete reproductive failure at levels as low as five ppm of the diet. Aroclor 1016 impaired reproduction less than Aroclor 1242. Although fewer females whelped and the four-week kit weights were less than the control animals, no outward signs of abnormalities beyond their smaller size were found in the kits whelped and nursed by dams fed Aroclor 1016. Ferrets were more resistant to the effects of either PCB mixture than were the mink, as noted by the lower mortality rate on the Aroclor 1242 diet and the almost normal level of reproduction on the Aroclor 1016 diet. Feeding Aroclor 1242 at 20 ppm resulted in complete reproductive failure, but was not fatal to adult ferrets. This finding is in sharp contrast to the 100% mortality of adult mink fed the same level. Although the chlorine content is similar in both compounds, Aroclor 1242 has a higher percentage of molecules with five or more chlorines per biphenyl. This difference in higher substituted biphenyl isomer content and/or the reduced levels of contaminants in the Aroclor 1016 mixture may be of major importance in evaluating the toxicity of these compounds.

Animals↗
PubMed1983

In vitro cytotoxicity of polychlorinated biphenyls (Aroclors 1016, 1242, 1254 and 1260) and their effect on phospholipid and neutral lipid composition of Chinese hamster ovary (CHO-K1) cells.

Cytotoxicity of 4 Aroclors (1016, 1242, 1254 and 1260) was compared in Chinese hamster ovary (CHO-K1) cells in Ham's F-12 medium. When parameters of toxicity were cell numbers or tissue protein, 50% lethality occurred at Aroclor concentrations between 30 and 45 ppm. An in vitro clonal assay with CHO-K1 cells was a sensitive indicator of cytotoxicity of the polychlorinated biphenyls (PCBs). From EC50 values (concentration that allowed 50% survival of formed colonies), cytotoxicity was lower with Aroclor 1016 (32 ppm) and higher with Aroclors 1254 (27 ppm) and 1260 (28 ppm). In cells exposed 24 h to a marginally cytotoxic dose (20 ppm) of each Aroclor, phospholipid (PL) thin-layer chromatography (TLC) showed an increase in phosphatidylcholine (PC) and a decrease in phosphatidylethanolamine (PE) and diphosphatidylglycerol (DPG). Neutral lipid (NL) TLC of cells given Aroclors 1242, 1254 or 1260 showed a 3-4-fold increase in triglyceride (TG) and a similar reduction in cholesteryl esters (CE); in contrast to Aroclor 1016 which produced no change in TG and a smaller (2-fold) reduction in CE. Cholesterol and free fatty acid fractions were unaffected by any of the Aroclors. The TG:PL ratio remained unchanged in cells given Aroclor 1016, but increased 3-4-fold with Aroclors 1242, 1254, or 1260. Compared to total values in the untreated controls, CHO-K1 cells contained less neutral lipid and more phospholipid only with Aroclor 1016. These results support the concept that differences in the behavior of Aroclor 1016 are related to its PCB composition. Changes in membrane PL and NL components, observed at marginally cytotoxic levels of each Aroclor, provided further evidence that the PCBs may affect membrane integrity and associated metabolic functions.

Animals↗
PubMedDate not supplied

Comparison of the effects of acute and subchronic administration of Aroclor 1254, a commercial mixture of polychlorinated biphenyls, on pentobarbital-induced sleep time and [14C]pentobarbital disposition in mice.

We have reported previously that polychlorinated biphenyls (PCBs) alter neurochemistry and suppress spontaneous locomotor activity in mice. The present study was initiated to determine whether orally administered (Aroclor 1254) would potentiate pentobarbital-induced sleep time. Sleep time was enhanced significantly by Aroclor 1254 (500 mg/kg) given 0 to 8 h prior to pentobarbital, with the peak effect occurring at 2 h. This effect was demonstrated to be dose-responsive in the range of 5 to 25 mg/kg given 2 h prior to pentobarbital, but only slightly larger increments in sleep time were observed with higher doses of PCBs (50, 100, 250, and 500 mg/kg). Administration of vehicle or Aroclor 1254 (30 or 100 mg/kg) for 14 successive days reduced sleep time when pentobarbital was given 45 min after the last dose of vehicle or Aroclor 1254, with a further reduction when pentobarbital was given 24 h after the last dose. As a correlate to the sleep-time studies, levels of pentobarbital and metabolites were measured in brain, liver, and plasma of mice that had received varying doses of Aroclor 1254 2 h prior to [14C]pentobarbital. Elevated levels of pentobarbital and decreased levels of metabolites were found after acute administration of Aroclor 1254 during a period of time when Aroclor 1254-treated mice were still asleep. These effects of Aroclor 1254 on pentobarbital disposition were found to be dose-dependent. Brain levels of pentobarbital in mice after 14 d of Aroclor 1254 treatment (30 mg/kg) were less than those in vehicle-treated animals, and these levels were consistent with the reduced sleep times. Thus, a correlation between pentobarbital brain levels and sleep time in both Aroclor 1254-treated and nontreated animals suggests that Aroclor 1254 does not alter pentobarbital narcosis by a direct action on the brain. Rather, acutely administered Aroclor 1254 may be augmenting sleep time by competing with pentobarbital for metabolic sites in the liver, while chronically administered Aroclor 1254 induces pentobarbital metabolism.

Animals↗
PubMed1998

Comparative carcinogenicity in Sprague-Dawley rats of the polychlorinated biphenyl mixtures Aroclors 1016, 1242, 1254, and 1260.

A comprehensive chronic toxicity and carcinogenicity study was conducted on a series of Aroclors (1016, 1242, 1254, and 1260). Each Aroclor was assessed at multiple dietary concentrations, ranging from 25 to 200 ppm, for 24 months in male and female Sprague-Dawley rats. Liver toxicity was indicated by elevated serum enzyme activity (AST, ALT, and GGT), elevated serum cholesterol concentration, decreases in hematologic parameters (RBC, Hb, and Hct), hepatocellular hypertrophy, an increased incidence of altered hepatocellular foci, and an increased incidence of hepatocellular neoplasms (primarily adenomas). Liver toxicity was distinctly more severe in females than in males. The incidence of hepatocellular neoplasms was highly sex-dependent (females >> males), differed between Aroclor mixtures and, for females, increased with dose and followed the general incidence pattern of Aroclor 1254 > Aroclor 1260 approximately Aroclor 1242 > Aroclor 1016. A significant response (p < 0.05) in males was seen only for the high dose of Aroclor 1260. A small increase in the incidence of thyroid gland follicular cell adenomas was noted in males for Aroclors 1242, 1254, and 1260, with the incidence being uniform across dose groups and Aroclor mixtures. For females, increased survival relative to controls was observed for all Aroclor treatment groups. A significantly decreased trend in the incidence of mammary gland neoplasms compared to control was also noted for females receiving Aroclors 1242, 1254, and 1260.

Animals↗
PubMed1987

Aroclor 1254 as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist: effects on enzyme induction and immunotoxicity.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor 1254 induced the cytochrome P-450 dependent monooxygenases, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) in rat hepatoma H-4-II E cells and C57BL/6J mice. It has been proposed that both Aroclor 1254 and 2,3,7,8-TCDD induce these enzymes via a common mechanism which features initial binding to the aryl hydrocarbon (Ah) cytosolic receptor protein. The major difference between these compounds was the relative potency (i.e. 2,3,7,8-TCDD much greater than Aroclor 1254). Cotreatment of rat hepatoma H-4-II E cells or C57BL/6J mice with a dose of 2,3,7,8-TCDD which submaximally induces AHH and EROD and a dose of Aroclor 1254 which exhibited little or no induction activity resulted in significant antagonism of the induction effects of 2,3,7,8-TCDD. For example, cotreatment of C57BL/6J mice with 2,3,7,8-TCDD (15 nmol/kg) and Aroclor 1254 (25, 75 and 150 mumol/kg) resulted in up to 23% antagonism of AHH induction by 2,3,7,8-TCDD. Moreover, cotreatment with a higher dose of the 2,3,7,8-TCDD agonist (30 or 50 nmol/kg) partially reversed some of the antagonism by Aroclor 1254. In vivo antagonism was observed only at Aroclor 1254/2,3,7,8-TCDD molar ratios of 1667:1, 5000:1 and 10,000:1. Administration of 2,3,7,8-TCDD (3.72 nmol/kg) to C57BL/6J mice resulted in a 76% decrease in the splenic plaque forming cell response to sheep red blood cells. This T-cell mediated immunotoxic effect of 2,3,7,8-TCDD segregates with the Ah locus. In contrast, administration of 5, 15, 75 and 150 mumol/kg of Aroclor 1254 resulted in impairment of the immune response only at the highest dose level. However, cotreatment of mice with 2,3,7,8-TCDD (3.72 nmol/kg) and Aroclor 1254 (5, 15 or 75 mumol/kg) resulted in no significant decrease in the plaque forming cell response and complete protection from the immunotoxicity of 2,3,7,8-TCDD. Cotreatment of the mice with Aroclor 1254 (75 mumol/kg) and a higher dose of the 2,3,7,8-TCDD agonist resulted in partial reversal of the protective effects of Aroclor 1254. The in vitro and in vivo data suggest that within specific antagonist/agonist dose ratios, Aroclor 1254 can antagonize at least 2 Ah receptor-mediated effects of 2,3,7,8-TCDD, namely AHH induction and immunotoxicity.

Animals↗
PubMed1995

Aroclor 1242 stimulates the production of inositol phosphates in polymorphonuclear neutrophils.

Exposure in vitro to the mixture of polychlorinated biphenyls (PCBs), Aroclor 1242, stimulates superoxide anion (O2-) production and degranulation in rat polymorphonuclear neutrophils (PMNs). The mechanism by which PCBs activate PMNs is unknown. Phospholipase C-dependent hydrolysis of membrane phosphoinositides is an important early event in PMN activation in response to several agonists including N-formyl-methionyl-leucyl phenylalanine (fMLP); therefore, the present study was undertaken to determine whether Aroclor 1242 stimulates the production of inositol phosphates in isolated rat PMNs. PMNs elicited with glycogen from rat peritoneum were labeled with myo-[2-3H]inositol, and the effect of fMLP and Aroclor 1242 on accumulation of [3H]inositol phosphates was determined. Both fMLP (in the presence of cytochalasin B) and Aroclor 1242 induced rapid breakdown of inositol-containing phospholipids. Peak accumulation of [3H]inositol phosphates occurred within 5 sec in response to Aroclor 1242 and within 15-30 sec in response to fMLP. In cytochalasin B-treated PMNs, significant O2- generation occurred within 5 min of exposure to fMLP or Aroclor 1242. 2,2',4,4'-Tetrachlorobiphenyl (TCB), but not 3,3',4,4'-TCB, stimulates O2- production and degranulation in isolated rat PMNs. To determine whether inositol phosphate accumulation parallels PMN activation, [3H]inositol monophosphate (IP) production was measured in response to Aroclor 1242, 2,2'4,4'-TCB, and 3,3'4,4'-TCB in LiCl-treated cells. Both Aroclor 1242 and 2,2',4,4'-TCB, but not 3,3',4,4'-TCB, caused significant accumulation of [3H]IP. Previous reports indicate that cytochalasin B enhances PMN activation in response to fMLP by increasing the production of inositol phosphates. Pretreatment of PMNs with cytochalasin B significantly enhanced O2- production in cells exposed to Aroclor 1242 but did not alter [H]IP accumulation. These data suggest that treatment of rat PMNs with Aroclor 1242 stimulates PI turnover and are consistent with the hypothesis that hydrolysis of membrane phospholipids is important in PMN activation by PCBs. The enhancing effect of cytochalasin B on PCB-induced O2- production, however, likely involves other mechanisms.

Amino Acid Sequence↗
PubMed1992

Induction of hepatic CYP1A in male F344/NCr rats by dietary exposure to Aroclor 1254: examination of immunochemical, RNA, catalytic, and pharmacokinetic endpoints.

Male F344/NCr rats were exposed to low dietary concentrations of Aroclor 1254 (0-33 ppm) for 7 days, following which the induction of selected hepatic drug metabolizing enzymes was monitored. CYP1A1, measured indirectly by assaying the O-dealkylation of ethoxyresorufin in 9000 g supernatants, was increased 1.5-, 3-, 8-, and 37-fold following 7 days of exposure to 1.0, 3.3, 10, and 33 ppm Aroclor, respectively. In contrast, the O-dealkylation of benzyloxyresorufin, an indirect measure of CYP2B1 activity, was increased approximately 4-fold following exposure to 33 ppm dietary Aroclor. Measurement of the non-P450-mediated activities epoxide hydrolase, DT-diaphorase, and aldehyde dehydrogenase (NADP+, benzaldehyde) revealed < 4-fold inductions following feeding of 33 ppm Aroclor. In view of the relatively high sensitivity of the CYP1A-specific catalytic endpoint as a biomarker for Aroclor exposure, alternative endpoints for detecting induction of this subfamily of P450 were also examined. The extent of in vivo CYP1A induction was assessed by measuring serum concentrations of zoxazolamine 150 min following an intraperitoneal dose of 100 mg/kg body wt. Slight decreases in serum zoxazolamine concentration were observed in rats exposed to as little as 1.0 ppm dietary Aroclor 1254, while profound decreases were seen in rats exposed to > or = to 10 ppm Aroclor. Immunodetection of CYP1A1 protein, with a monoclonal antibody directed against this cytochrome, revealed a 2.9-fold increase in rats exposed to as little as 1.0 ppm Aroclor, and approximately 10- and 44-fold increases following exposure to 3.3 and 10 ppm dietary Aroclor, respectively. Increases in total hepatocellular RNA coding for CYP1A1 and CYP1A2, quantified by hybridization to specific oligonucleotide probes, corresponded well to the increases in hepatic O-dealkylase activity for ethoxyresorufin (CYP1A1) and methoxyresorufin (CYP1A2), respectively. Thus, CYP1A induction, directly or indirectly measured with a variety of endpoints, represents a highly sensitive biomarker for exposure to relatively low doses of Aroclor 1254 in the rat.

Administration, Oral↗
PubMed1993

Comparative potencies of Aroclors 1232, 1242, 1248, 1254, and 1260 in male Wistar rats--assessment of the toxic equivalency factor (TEF) approach for polychlorinated biphenyls (PCBs).

Immature male Wistar rats were treated with several different doses of the commercial polychlorinated biphenyls (PCBs) Aroclors 1232, 1242, 1248, 1254, and 1260 (10, 40, 160, 480, and 2000 mg/kg) and the effects on body weight gain, thymic atrophy, and the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH), ethoxyresorufin O-deethylase (EROD), and pentoxyresorufin O-deethylase (PROD) activities were measured 14 days after treatment. A significant inhibition in body weight gain was observed only in rats treated with high doses of Aroclors 1232 and 1248 and thymic atrophy was not observed for any of the Aroclors. All the Aroclors caused a dose-dependent increase in hepatic microsomal AHH, EROD, and PROD activities. The corresponding ED50 values for the induction of AHH-EROD activities varied from 51 to 678 mg/kg. Aroclor 1260 was the least active inducer of the P4501A1-mediated enzyme activities. In contrast, Aroclor 1260 was a potent inducer of PROD activity (ED50 = 37 mg/kg), but Aroclors 1232, 1242, 1248, and 1254 did not induce 50% of the maximal response at the highest dose used in this experiment (2000/kg). Previous studies have quantitated the levels of those PCB congeners which induce AHH or EROD activities in Aroclors 1232, 1242, 1254, and 1260 and their potencies or toxic equivalency factors (TEFs) relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have also been estimated or experimentally determined. Using highly conservative TEF values it was demonstrated that the calculated ED50s for the Aroclors as inducers of AHH and EROD activity were significantly lower than the observed ED50 values.2

Animals↗
PubMed1977

Inhibitory effect of a polychlorinated biphenyl (Aroclor 1254) on aflatoxin B1 carcinogenesis in rainbow trout (Salmo gairdneri).

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. Appropriate controls were also maintained. Samples were taken at 1, 2, 4, 6, 9, and 12 months to monitor tumor incidence, Aroclor 1254 accumulation, and histopathology of liver, spleen, and kidney tissues. 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. None of the control or Aroclor 1254-fed fish had liver tumors. Levels of Aroclor 1254 increased rapidly during the first 6 months, then plateaued at approximately 80 ppm on a whole-fish basis. AFB1 inhibited growth but Aroclor 1254 did not. Glycogen depletion of hepatocytes and hyperemia, and white pulp depletion of the spleen were the only changes induced by Aroclor 1254.

Aflatoxins↗
PubMed1985

Aroclor 1254 pretreatment effects on DNA repair in rat hepatocytes elicited by in vivo or in vitro exposure to various chemicals.

Inducers of liver mixed function oxidase (MFO) activities have profound effects on the genotoxicity of substances that undergo metabolic activation by the MFO system. The polychlorinated biphenyl mixture Aroclor 1254 is a broad-spectrum inducer of liver MFO activities that has been employed as a pretreatment to augment the metabolic activation capabilities of rat liver fractions used in a number of short-term tests for genotoxicity, including the Ames Salmonella/bacterial mutagenicity assay. The present study was designed to characterize the effects of Aroclor pretreatment of rats on the DNA repair responses elicited by various chemicals in the in vitro hepatocyte primary culture/DNA repair (HPC/DR) assay as well as the in vivo/in vitro HPC/DR assay. The amount of DNA repair produced in vitro by diethylnitrosamine (DEN), benzo(a)pyrene (B(a)P), 3-methylcholanthrene (3-MC), 2-acetylaminofluorene (2-AAF), o-aminoazotoluene (o-AT), and aflatoxin B1 (AFB1) was significantly greater in hepatocytes derived from Aroclor-pretreated rats than in control rat hepatocytes; in vitro responses to dimethylnitrosamine (DMN), 7,12-dimethylbenzanthracene (DMBA), benzidine (BZ), and 2-naphthylamine (2-NA) were not significantly affected by Aroclor pretreatment. DNA repair elicited by the direct-acting alkylating agents methyl methanesulfonate and N-methyl-N'-nitro-N-nitrosoguanidine was also not increased by Aroclor pretreatment, which indicated that Aroclor does not exert a general stimulatory effect on the hepatocellular DNA repair capacity. Therefore, the pretreatment-related potentiation of DNA repair observed for 6 out of 12 compounds tested in vitro was considered to be due to enhanced metabolic activation. These results suggested that pretreatment with Aroclor may increase the sensitivity of the in vitro HPC/DR assay to certain compounds. In contrast, Aroclor pretreatment had little effect on the amount of hepatocellular DNA repair elicited by in vivo administration of DMN, DEN, o-AT, 2-AAF, 3-MC, or AFB1, which indicated that this pretreatment regimen may have little utility for improving the sensitivity of the in vivo/in vitro HPC/DR assay.

Animals↗