title: Heme biosynthesis pathway regulation in a model of hepatocarcinogenesis pre-initiation.
abstract: 1. Heme regulation before the appearance of hyperplastic nodules was investigated in mice models of hepatocarcinogenesis. 2. With this aim 5-aminolaevulinate synthetase (ALA-S), microsomal heme-oxygenase (MHO), mitochondrial and cytoplasmic rhodanese activities were examined throughout a period of 35 days in animals exposed to dietary p-dimethylaminoazobenzene (DAB). 3. ALA-S activity was significantly diminished (50%) on day 14, then showing a sharply rising profile from day 28 onwards, and reaching 350% on day 35. 4. A similar profile was observed for mitochondrial rhodanese activity. 5. Changes in MHO and cytoplasmic rhodanese activities were almost the opposite to those observed for ALA-S. 6. The distinctive alteration in mitochondrial and cytoplasmic rhodanese would suggest that it plays a subtle role in ALA-S regulation during carcinogenesis initiation through a mechanism that appears to involve subcellular localization controls perhaps by means of the breakage of cystine trisulphide postulated to act as an ALA-S activator. 7. Taking into account the present results, we suggest a probable mechanism for the onset of hepatocarcinogenesis that includes a primary activating liver status, provoking biochemical aberration leading to the stage of initiation of hepatocarcinogenesis involving the whole organ.
authors.affiliation: Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET y FCEN, UBA, Ciudad Universitaria, Republic of Argentina.
authors.forename: C F
authors.initials: CF
authors.lastname: Polo
authors.forename: E S
authors.initials: ES
authors.lastname: Vazquez
authors.forename: F
authors.initials: F
authors.lastname: Caballero
authors.forename: E
authors.initials: E
authors.lastname: Gerez
authors.forename: A M
authors.initials: AM
authors.lastname: Battle
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D003593:Cytoplasm / Q000201:enzymology; D006418:Heme / Q000096:biosynthesis*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism; D004124:p-Dimethylaminoazobenzene
chemical_list: D006418:Heme; D004124:p-Dimethylaminoazobenzene; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase; D013884:Thiosulfate Sulfurtransferase