Modulation of hepatic heme-binding Z protein in mice by the porphyrogenic carcinogens griseofulvin and hexachlorobenzene.
Some reports link human hepatic porphyria with a risk of hepatocellular carcinoma. Hepatic protoporphyria and uroporphyria were induced in mice by feeding griseofulvin and hexachlorobenzene (HCB), respectively. These chemicals also cause liver cancer. Hepatic immunoreactive cytosolic levels of heme-binding Z protein (HBP) were reduced by 81% (griseofulvin) and 55% (HCB). In contrast, both treatments caused a greater than 4-fold increase in the immunoreactive levels of glutathione S-transferase isozymes (GST) which like HBP also bind heme. Unlike in vitro studies in the presence of porphyrins, no cross-linking of HBP was observed in vivo.
Vincent
S H
SH
Department of Pediatrics, Cornell University Medical College, New York Hospital, NY 10021.
Smith
A G
AG
Muller-Eberhard
U
U
D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D002722:Chlorobenzenes / Q000494:pharmacology*; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D006118:Griseofulvin / Q000494:pharmacology*; D006418:Heme / Q000378:metabolism*; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D006581:Hexachlorobenzene / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D011164:Porphyrias / Q000139:chemically induced / Q000378:metabolism*
D002273:Carcinogens; D002352:Carrier Proteins; D002722:Chlorobenzenes; D003432:Cross-Linking Reagents; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D006118:Griseofulvin; D006418:Heme; D006581:Hexachlorobenzene