Promotion of enzyme altered foci in female rat 2,3,3',4,4',5-hexachlorobiphenyl.
The tumor promoting activity of 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) was studied in an initiation/promotion bioassay in female Sprague-Dawley rats initiated with N-nitrosodiethylamine after partial hepatectomy. PCB 156 (50, 300, 1500, or 7500 microg/kg body weight/week) was administered by once-weekly subcutaneous injections for 20 weeks. Some high dose animals were left without treatment for an additional 20 weeks to study posttreatment effects. The volume fraction of the liver occupied by glutathione S-transferase P-positive foci was significantly increased to 2.9, 3.3, and 12% at 300, 1500, and 7500 microg/kg body weight/week, respectively, compared to 1.2% in the controls. The volume fraction was 43% in the high dose group 20 weeks after treatment was stopped, probably reflecting the slow body clearance of PCB 156 as indicated by the sustained liver and adipose tissue concentrations. Treatment with PCB 156 following initiation caused decreased body weight gain, thymic atrophy, liver enlargement, induction of hepatic cytochrome P450 1A1/2 (CYP1A1/2) and CYP2B1/2 activities, histopathological effects, and increased activities of aspartate aminotransferase and gamma-glutamyltransferase in plasma. These results show that PCB 156 can enhance the growth of altered foci in rat liver and probably act as a tumor promoter of hepatocarcinogenesis. Based on promotional activity a relative potency of PCB 156 to 2,3,7, 8-tetrachlorodibenzo-p-dioxin of 0.0001-0.001 is proposed.
Haag-Grönlund
M
M
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, S-171 77, Sweden.
Kato
Y
Y
Fransson-Steen
R
R
Scheu
G
G
Wärngârd
L
L
D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002273:Carcinogens / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D006498:Hepatectomy; D007279:Injections, Subcutaneous; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects; D005723:gamma-Glutamyltransferase / Q000097:blood
D002273:Carcinogens; C087667:2,3,3',4,4',5-hexachlorobiphenyl; D004052:Diethylnitrosamine; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases