الفهرس 
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Abstract
The aim of the present studies was to describe the promoting effect of two organochlorine pesticides: Heptachlore (HEP) and hexachlorobenzene (HCB), using medium term hepatocarcinogenesis liver bioassay which proposed in the literature to be useful endpoints in screening of non-genotoxic hepatocarcinogens and/or liver tumor promoters. We investigated the effects on the following endpoints: hepatomegaly, GST-P foci areas and numbers as well as cytochrome CYP2B1/2, CYP3A1/2 mRNA induction, IkB and NF-kB transcription factors. Male F 344 rats received HCB in two different doses 70, 350 ppm, and HEP at a daily oral dose of 5, 25 ppm, and combination of both HEP and HCB at either at low or high doses. When both pesticides applied separately, nonsignificant increased of GST-P positive foci areas and numbers as compared with DEN control treated group was noticed. However their mixture at low dose showed an additive effect. In between high doses treated groups, only HCB treated rats at 350ppm demonstrated significant increase of GST-P positive foci areas and numbers as compared with DEN control treated group although HEP treated at 25ppm was non significant. Promotional synergistic effect was noticed in combination group treated with both HEP and HCB (25 and 350 ppm respectively) when compared with HEP (25 ppm) or HCB (350 ppm) treated groups. Cytochrome P450 2B1 and 3A1 mRNA overexpression as well as IkB and NF-kB transcription factors were correlated well with the number and area of GST-P positive foci. These results support evidence of additive promoting potentials of both HEP and HCB and also indicate a carcinogenic potential for some organochlorines mixture may exist regarding rat liver carcinogenesis.