Study of the separate and combined effects of the non-planer 2,5,2′,5′-and the planner 3,4,3′,4′-tetrachlorobiphenyl in liver and lymphocytes in vivo

Abstract

Polychlorinated biphenyls (PCBs) are a group of industrial chemicals that are widely distributed in the environment. Because these compounds occur as mixtures, studies of their possible interactive effects are essential for an understanding of the mechanism of the toxicity of these mixtures. For the determination of a possible interaction of the effects in vivo of 2,5,2',5'-tetrachlorobiphenyl (TCB) and 3,4,3',4'-TCB, rats were exposed to a single dose of diethylnitrosamine (DEN) and subsequently to 0.1 p.p.m. 3,4,3',4'-TCB and/or 10 p.p.m. 2,5,2',5'-TCB in the feed for 1 year. The two major targets of PCB toxicity, the liver and the peripheral blood, were examined after these treatments. TCB treatment after DEN exposure caused a predominance of increased placental glutathione S-transferase (PGST) and deficiencies of ATPase as preneoplastic markers in focal hepatic lesions. When 0.05% phenobarbital (PB) was administered after DEN exposure, the distribution of markers in altered hepatic foci (AHF) was essentially equal for increased PGST and gamma-glutamyltranspeptidase (GGT) and for ATPase deficiency. Many of these AHF also exhibited increased P450 b/e expression. Our results demonstrated that the two PCB congeners interacted in vivo to produce an increase in AHF that were PGST positive and ATPase negative. PGST-positive and ATPase-negative AHF correlated best with focal areas of P450 b/e expression. The combination of the two PCBs caused a greater than additive decrease in the total number of lymphocytes and antibody-producing B-cells. Also the thymocyte-dependent T-helper cells isolated from the animals receiving the combination of TCBs demonstrated a morphologically abnormal subpopulation. The results indicate that the interaction of 2,5,2',5'-TCB and 3,4,3',4'-TCB in vivo induced much greater toxicity and mutagenicity in peripheral lymphocytes and hepatocytes than treatment with either congener alone.

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

“…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).…”

Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure

“…It has been suggested that this route of PCB metabolism could form semi-quinone radicals which could mediate cytotoxicity by leading to increased intracellular steady-state levels of O 2 ·− and H 2 O 2 [39]. Since ROS are known to play a role in both mitogenesis and genomic instability [12], which may contribute to carcinogenesis, it has been proposed that PCB-induced metabolic oxidative stress contributes to neoplastic transformation [7, 8, 40, 41] and other deleterious effects of PCBs and their metabolites [5, 7, 8, 14]. However, despite the interest in PCB-induced oxidative stress there is very little direct evidence in living cells identifying the specific ROS involved in mediating PCB induced cell injury or identifying the intracellular sites of ROS production.…”

Airborne polychlorinated biphenyls (PCBs) reduce telomerase activity and shorten telomere length in immortal human skin keratinocytes (HaCat)

“…PCB 52 was shown to induce DNA damage in cultured human lymphocytes (Sandal et al , 2008) and to induce and promote tumors in rat liver (Espandiari et al, 2003; Preston et al, 1985). Highly interesting is that PCB 52 acted synergistically with PCB 77 with respect to genotoxic and cancer initiating activity (Meisner et al, 1992; Sargent et al, 1991; Sargent et al, 1989). It should be considered, however, that these experiments were done with single/few/short term exposures to high doses/concentrations, a completely different scenario than our daily long term low dose exposure through air and food.…”