Relative tumour promoting activity of three polychlorinated biphenyls in rat liver

Hemming, H. G.; Flodström, Sten; Wärngård, Lars; Bergman, Åke; Kronevi, Tony; Nordgren, Ingrid; Ahlborg, Ulf G.

doi:10.1016/0926-6917(93)90039-s

Cited by 25 publications

(31 citation statements)

References 44 publications

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“…The macroscopic lesions and tumors found after 52 weeks of treatment give further support to this conclusion. These results are in agreement with other studies in which both coplanar and nonplanar PCBs have been shown to act as tumor promoters by enhancing the development of preneoplastic lesions and tumors in rats and mice after treatment with various mutagens Buchmann et ai, 1991;Sargent et al, 1991;Hemming et al, 1993).…”

Section: Discussionsupporting

confidence: 83%

“…Thus, this parameter is a relevant endpoint for assessing the tumor promotive potential of a chemical (Ito et al, 1992). As expected, the positive control compound PCB-126 was a very potent enhancer of the volume fraction of altered hepatic foci (Hemming et al, 1993). PCB-118 did not increase the volume fraction of GST-P-positive foci significantly at any of the dose levels after 20 weeks, but there was a tendency toward higher values with increasing dose (Fig.…”

Section: Discussionmentioning

confidence: 68%

“…The initiated animals were allowed to recover for 5 weeks before the promotion period started. At that time the animals were allocated at random to one vehicle control group and to seven treatment groups subcutaneously injected either with 10 /zg PCB-126/kg body weight/ week, which was used as a positive control (Hemming et al, 1993), or with 10, 40, 160. 640.…”

Section: Methodsmentioning

confidence: 99%

“…Activities were assayed fluorimetncally in S-9 mix (0.02-0.2 mg protein) at 37°C using a Shimadzu RF-5000 spectrofluorophotometer as essentially reported by Lubet et al (1985) and Hemming et al (1993). Activities of yglutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined in blood plasma by standard kinetic assay kits (Boehringer Mannheim GmbH, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast to the coplanar PCBs, less and nonplanar PCBs with some degree of ortho substitution bind less potently to the Ah receptor (Bandiera et al, 1982;Safe, 1990). These types of PCBs are also believed to have tumor promotive effects (Hemming et al, 1993), and the Ah receptor is assumed to play some role in this process. However, the mode of action in carcinogenicity for these ortho substituted congeners is less known at present, although inhibition of gap junctional communication may be one contributing mechanism (Hemming et al, 1991).…”

mentioning

confidence: 99%

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Promotion of Altered Hepatic Foci by 2,3′,4,4′,5-Pentachlorobiphenyl in Sprague-Dawley Female Rats

et al. 1997

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The tumor promotion potential of 2,3',4,4',5-pentachlorobiphenyl (PCB-118) was studied in a two-stage initiation/promotion bioassay in female Sprague-Dawley rats. The animals were initiated by intraperitoneal administration of iV-nitrosodiethylamine after partial hepatectomy. After 5 weeks of recovery, the promotion period commenced by once-weekly subcutaneous administrations of PCB-118 at six dose levels (10, 40, 160, 640, 2500, and 10,000 /ig/kg body weight/week) for 20 weeks. In addition, three of these dose levels (40, 640, and 10,000 ^g/kg body weight/week) were administered for 52 weeks. Evaluation of hepatic foci positive for glutathione S-transferase P demonstrated that the mono-ortho chlorine substituted congener PCB-118 significantly increased the number of foci/cm 3 of liver in the two highest dose groups after 20 weeks, but did not significantly increase the percentage of the liver occupied by foci. After 52 weeks of treatment, both the percentage and the number of foci/cm 3 were significantly increased in the highest dose group. A toxic equivalency factor based on foci development during 20 weeks of treatment would be less than 0.00002. Altered relative liver and thymus weights were observed after treatment with both substances as well as an induction of methyl cholanthrene-and phenobarbital-inducibie isoenzymes of cytochrome P450 monooxygenase. These results show that PCB-118 has a potency to enhance foci growth in rat liver, although the potency is low compared to that of structurally related compounds. © 1997 Society of Toxicology.As a result of an extended, worldwide, and regular use of commercial mixtures of polychlorinated biphenyls (PCBs), these persistent compounds are widely spread in the environment. In many countries this use is nowadays restricted and

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Promotion of Altered Hepatic Foci by 2,3′,4,4′,5-Pentachlorobiphenyl in Sprague-Dawley Female Rats

et al. 1997

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2005

EFSA Journal

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SUMMARYPolychlorinated biphenyls (PCB) cover a group of 209 different PCB congeners which can be divided into two groups according to their toxicological properties. One group, consisting of 12 congeners, show toxicological properties similar to dioxins, is therefore termed "dioxinlike PCB" (DL-PCB), and these have been included in the "Risk Assessment of Dioxins and Dioxin-Like PCBs in Food" performed by the EU Scientific Committee on Food (SCF). The other PCB, referred to as "non dioxin-like PCB" (NDL-PCB), have not been previously evaluated by the SCF or EFSA. Both groups of PCB, NDL-PCB as well DL-PCB, are usually found in feed and food.PCB were widely used in a number of industrial and commercial applications. It is estimated that more than 1 million tons of technical PCB mixtures were produced world-wide since their first commercial use in the late 1920s. Although produced by comparable production processes, technical PCB mixtures contain both DL and NDL-PCB and may vary considerably with respect to their congener composition due to differences in the amount of chlorine and the reaction conditions applied. Moreover, technical PCB mixtures contain other dioxin-like compounds as impurities, such as polychlorinated dibenzofurans (PCDF). The different compositions as well as the presence of toxicologically relevant impurities may have a significant impact on the results of toxicological studies with technical PCB mixtures.Although the manufacture, processing and distribution of PCB has been prohibited in almost all industrial countries since the late 1980s, their entry into the environment still occurs, especially due to improper disposal practices or leaks in electrical equipment and hydraulic systems still in use. PCB are highly persistent and are globally circulated by atmospheric transport and thus are present in all environmental media.Data on the occurrence of NDL-PCB in food and feed have been reported in different ways for example as the sum of three PCB congeners (PCB 138, 153 and 180), as the sum of six PCB congeners (PCB 28, 52, 101, 138, 153, 180) often referred to as indicator PCB or as the sum of seven (sum of six indicator PCB plus PCB 118). This lack of consistency often hampers a direct comparison of occurrence data. The Panel decided to use the sum of the six indicator PCB as the basis for the evaluation in this opinion, because these congeners are appropriate indicators for different PCB patterns in various sample matrices and are most suitable for a risk assessment of NDL-PCB on the basis of the available data. The Panel noted that the sum of the six indicator PCB represents about 50% of total NDL-PCB in food.Following exposure of farm animals, NDL-PCB will accumulate in meat, liver and particularly in fat tissues. In addition, NDL-PCB will be transferred into milk and eggs, and levels in these products will reach a steady state following exposure over a period of several weeks. PCB 138 and 153, both with six chlorine atoms, show the highest carry-over into milk and eggs, in the order of 5...

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Interactive Effects of Three Structurally Different Polychlorinated Biphenyls in a Rat Liver Tumor Promotion Bioassay

Haag‐Grönlund

Johansson

Fransson-Steen³

et al. 1998

Toxicology and Applied Pharmacology

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Relative tumour promoting activity of three polychlorinated biphenyls in rat liver

Cited by 25 publications

References 44 publications

Promotion of Altered Hepatic Foci by 2,3′,4,4′,5-Pentachlorobiphenyl in Sprague-Dawley Female Rats

Promotion of Altered Hepatic Foci by 2,3′,4,4′,5-Pentachlorobiphenyl in Sprague-Dawley Female Rats

Untitled

Interactive Effects of Three Structurally Different Polychlorinated Biphenyls in a Rat Liver Tumor Promotion Bioassay

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