Promotion of altered hepatic foci by 2,3',4,4',5-pentachlorobiphenyl in Sprague-Dawley female rats.
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 N-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 microg/kg body weight/week) for 20 weeks. In addition, three of these dose levels (40, 640, and 10,000 microg/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/cm3 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/cm3 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-inducible 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.
Haag-Grönlund
M
M
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Wärngård
L
L
Flodström
S
S
Scheu
G
G
Kronevi
T
T
Ahlborg
U G
UG
Fransson-Steen
R
R
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006498:Hepatectomy; D007279:Injections, Subcutaneous; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D000637:Transaminases / Q000097:blood
C070055:2,3',4,4',5-pentachlorobiphenyl; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D005982:Glutathione Transferase; D000637:Transaminases; C023035:3,4,5,3',4'-pentachlorobiphenyl