titoli, abstracts, parole chiave >>>
Long-term dehydroepiandrosterone and 16-fluoro-5-androsten-17-one administration enhances DNA synthesis and induces expression of c-fos and c-Ha-ras in a selected population of preneoplastic lesions in liver of diethylnitrosamine-initiated rats

Simile, Maria Maddalena and De Miglio, Maria Rosaria and Calvisi, Diego Francesco and Muroni, Maria Rosaria and Frau, Maddalena and Asara, Giuseppina and Daino, Lucia and Deiana, Luca and Pascale, Rosa Maria and Feo, Francesco (2001) Long-term dehydroepiandrosterone and 16-fluoro-5-androsten-17-one administration enhances DNA synthesis and induces expression of c-fos and c-Ha-ras in a selected population of preneoplastic lesions in liver of diethylnitrosamine-initiated rats. Carcinogenesis, Vol. 22 (2), p. 301-308. ISSN 1460-2180. Article.

Full text not available from this repository.

Alternative URLs:

Abstract

Dehydroepiandrosterone (DHEA) inhibits glucose 6-phosphate dehydrogenase (G6PD) activity and growth of preneoplastic lesions in various tissues, but its administration may also enhance tumorigenesis by genotoxic carcinogens. We have investigated in single preneoplastic liver lesions, induced in diethylnitrosamine-initiated rats by the resistant hepatocyte protocol, the mechanisms underlying these opposite DHEA effects. Administration of DHEA (0.45% in the diet) for 10 and 26 weeks and of its analog 16 -fluoro-5-androsten-17-one (FA, 0.25%) for 10 weeks, starting 4 weeks after initiation, induced an apparent decrease in the number of glutathione S-transferase (placental) (GST-P)-positive lesions and an increase in lesion volume. DHEA administration for 38 weeks enhanced hepatocellular carcinoma multiplicity. Depending on the rise in the number of slowly growing, remodeling GST-P-positive lesions induced by DHEA and FA, overall DNA synthesis decreased slightly in these lesions at 14 weeks, but increased in uniform lesions. Labeling index (LI) in single uniform lesions at 14 weeks ranged between very low (not different from normal liver) to high (>10-fold normal liver). DHEA and FA induced broad increases in lesions with a high LI, which showed a higher number of cells overexpressing c-Ha-ras and/or c-fos than those with a lower LI. High G6PD activity was inhibited by DHEA and FA in only ~50% of preneoplastic lesions. These data indicate selection in rats subjected to long-term DHEA and FA treatments of a subpopulation of GST-P-positive cells with high growth and progression potentials. Overall effects of these compounds depends on the relative numbers of lesions in which inhibition of DNA synthesis can counteract their transforming effect.

Item Type:Article
ID Code:4325
Status:Published
Refereed:Yes
Uncontrolled Keywords:Induced lipid-peroxidation, n-nitrosomorpholine, analog 16-alpha-fluoro-5-androsten-17-one, experimental carcinogenesis, peroxisome proliferation, phenotypic modulation, transcription factor, lung carcinogenesis, rainbow-trout, female rats
Subjects:Area 05 - Scienze biologiche > BIO/12 Biochimica clinica e biologia molecolare clinica
Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Oxford University Press
ISSN:1460-2180
Deposited On:23 Aug 2010 09:22

I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore

Repository Staff Only: item control page