Altered heme pathway regulation and drug metabolizing enzyme system in a mouse model of hepatocarcinogenesis: effect of veronal.
1. Male CF 1 mice were fed p-dimethylaminoazobenzene (DAB) for 35 days and received 5,5-diethylbarbituric acid, before or after DAB treatment, with the purpose of investigating whether the onset of the preinitiation stage of carcinogenesis alters the natural regulatory mechanism of the heme pathway. 2. Changes detected in drug metabolizing enzymes are likely to be the consequence of a primary deregulation mechanism of heme metabolism, shown by an increase in delta-aminolevulinic acid synthetase activity and a decrease in microsomal heme oxygenase, which would finally lead to a great enhancement of cytochrome P450 levels. 3. The alterations found here would give rise to a pattern distinctive to that usually observed in the so-called resistant hepatocyte.
Gerez
E
E
Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), (CONICET-FCEN, UBA), Ciudad Universitaria, Buenos Aires, Argentina.
Vazquez
E
E
Caballero
F
F
Polo
C
C
Batlle
A
A
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D001462:Barbital / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006418:Heme / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D011230:Precancerous Conditions / Q000503:physiopathology; D013429:Sulfatases / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000378:metabolism; D004124:p-Dimethylaminoazobenzene
D006418:Heme; D001462:Barbital; D003577:Cytochrome P-450 Enzyme System; D004124:p-Dimethylaminoazobenzene; D002374:Catalase; D014366:Tryptophan Oxygenase; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase; D005982:Glutathione Transferase; D013429:Sulfatases; D005966:Glucuronidase