Journal Article

Cell proliferation induced by 3,3′,5-triiodo-L-thyronine is associated with a reduction in the number of preneoplastic hepatic lesions

G.M. Ledda-Columbano, A. Perra, R. Piga, M. Pibiri, R. Loi, H. Shinozuka and A. Columbano

in Carcinogenesis

Volume 20, issue 12, pages 2299-2304
Published in print December 1999 | ISSN: 0143-3334
Published online December 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.12.2299
Cell proliferation induced by 3,3′,5-triiodo-L-thyronine is associated with a reduction in the number of preneoplastic hepatic lesions

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Previous studies have suggested that liver cell proliferation is fundamental for the growth of carcinogen-initiated cells. To gain further information on the association between cell proliferation and hepatocarcinogenesis, we have examined the effect of the hormone 3,3′,5-triiodo-L-thyronine (T3), a strong liver mitogen, on the growth of diethylnitrosamine (DENA)-induced hepatic lesions positive for the placental form of glutathione S-transferase (GSTP). Two weeks after a single initiating dose of DENA (150 mg/kg), cycles of liver cell proliferation were induced in male Fischer rats by feeding a T3-supplemented diet (4 mg/kg) 1 week/month for 7 months. Rats were killed at the end of the seventh cycle or 1 month later. Results indicate that, in spite of an increased labelling index, a 70% reduction in the number/cm2 of GSTP-positive minifoci occurred in T3-treated rats. A decrease in the number of GSTP-positive foci was also observed in T3-treated rats killed 1 month after the last exposure to the hormone (40, versus 67 foci/cm2 in controls), indicating that the reduction was not due to an inhibitory effect on GSTP exerted by the concomitant presence of T3. In a second series of experiments where DENA-treated rats were fed T3 for 1 week and then subjected to the resistant hepatocyte (RH) model, it was found that T3 treatment prior to promotion resulted in a decrease in the number of GSTP-positive foci (16 GSTP+ foci/cm2 in T3-fed animals versus 45 in the control group). The results indicate that cell proliferation associated with T3 treatment: (i) reduces the number of carcinogen-induced GSTP-positive lesions; (ii) does not exert any differential effect on the growth of the remaining foci; (iii) inhibits the capacity of putative DENA-initiated cells to be promoted by the RH model. Data suggest that cell proliferation may not necessarily represent a stimulus for the growth of putative preneoplastic lesions.

Keywords: 2-AAF, 2-acetylaminofluorene; BrdU, bromodeoxyuridine; DENA, diethylnitrosamine; GSTP, glutathione S-transferase placental form; LI, labelling index; PH, partial hepatectomy; PP, peroxisome proliferators; PPAR, peroxisome proliferator-activated receptor; RH, resistant hepatocyte; RXR, retinoic acid receptor; T3, 3,3′,5-triiodo-l-thyronine; TR, T3 receptor.

Journal Article.  4921 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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