Nuclear Lesions During Rat Hepatocarcinogenesis. II. Measuring the Micronuclei During Initiation, Promotion and Progression of Rat Hepatocarcinogenesis Induced with DiethylnitrosamineHerens, Christian ; Massart, Sandrina ; et alin Mutation Research : Fundamental & Molecular Mechanisms of Mutagenesis (1995), 329(2), 161-71 We reported in our companion paper the strong correlation between elevated sister-chromatid exchange (SCE) frequencies and the initiation step of rat hepatocarcinogenesis. We have also shown that SCEs ... [more ▼] We reported in our companion paper the strong correlation between elevated sister-chromatid exchange (SCE) frequencies and the initiation step of rat hepatocarcinogenesis. We have also shown that SCEs return to normal values during the promotion and the progression stages. In the present study, we evaluated the clastogenic activity of diethylnitrosamine (DEN) during initiation, promotion and progression of rat hepatocarcinogenesis. We measured, at various times after DEN administration, the number of micronuclei (MN) produced by the mitotic response to partial hepatectomy. The results established that the DEN treatment induces a great number of preclastogenic lesions. In subcarcinogenic conditions (initiation alone), the number of MN expressed after partial hepatectomy remains high regardless of the time interval between the end of the DEN treatment and the operation. In this condition, the preclastogenic lesions persist for up to 1 year after the DEN administration is discontinued. Conversely, in carcinogenic conditions (initiation + promotion + progression), the number of MN expressed after partial hepatectomy decreases during the promotion and progression stages. These observations indicate that promotion and progression but not initiation are associated with the expression of persistent preclastogenic lesions, resulting in the production of chromosomally abnormal hepatocytes. [less ▲] Detailed reference viewed: 3 (2 ULg) Importance of Cell Kinetics Rhythmicity for the Control of Cell Proliferation and Carcinogenesis in Rat Liver (Review)Barbason, Hervé ; Herens, Christian ; et alin In Vivo (Athens, Greece) (1995), 9(6, Nov-Dec), 539-48 The circadian control of cell Proliferation and Differentiation has been studied principally in rat liver. The comparison between the differentiation by hepatic enzymes and the division by the cell cycle ... [more ▼] The circadian control of cell Proliferation and Differentiation has been studied principally in rat liver. The comparison between the differentiation by hepatic enzymes and the division by the cell cycle under various experimental conditions (postnatal maturation, regeneration after partial hepatectomy, adrenalectomy, corticosterone treatments etc.) leads to the following conclusions: Under physiological conditions, proliferation and differentiation activities present a mutually exclusive relationship with a specific circadian rhythm. For both functions, the circadian variation of corticosterone plays the role of synchronizer, each evening (peak) it induces the synthesis of tissue specific enzymes in G0 cells and simultaneously inhibits the DNA synthesis in cycling cells. The same parameters have been studied during the different stages of hepatocarcinogenesis induced by Diethylnitrosamine (DEN). After initiation alone, (DEN for 2 weeks) circadian control is unchanged and precancerous cells are not able to reach malignancy. Promotion (DEN for 6 weeks) consists of disturbing the circadian synchronization to liberate the selective growth of initiated precancerous cells. This proliferation advantage favours the accumulation of chromosomal aberrations including those implicated in malignant transformation: i.e. activation of oncogenes or inhibition of antioncogenes. [less ▲] Detailed reference viewed: 20 (1 ULg) Strychnopentamine, a Potential Anticancer Agent; ; et al in Planta Medica (1993), 59(1), 59-62 We analysed the effects of strychnopentamine, an alkaloid isolated from Strychnos usambarensis, on an Ehrlich ascites tumor growing in the mouse after inoculation. Four subcutaneous injections of 1.5 mg ... [more ▼] We analysed the effects of strychnopentamine, an alkaloid isolated from Strychnos usambarensis, on an Ehrlich ascites tumor growing in the mouse after inoculation. Four subcutaneous injections of 1.5 mg strychnopentamine (1 per day) induce a significant decrease of the number of tumor cells and a significant increase of the survival of the treated mice. Observed side effects are partial haemolysis and some liver damage. [less ▲] Detailed reference viewed: 14 (4 ULg) Circadian Synchronization of Liver Regeneration in Adult Rats: The Role Played by Adrenal HormonesBarbason, Hervé ; ; Herens, Christian et alin Cell and Tissue Kinetics (1989), 22(6), 451-60 The role played by the adrenal hormones in the regulation of liver proliferation in adult rats was investigated under various experimental conditions. In untreated control groups, cell growth was very low ... [more ▼] The role played by the adrenal hormones in the regulation of liver proliferation in adult rats was investigated under various experimental conditions. In untreated control groups, cell growth was very low and endogenous corticosterone levels showed a clearly-defined circadian rhythm with a peak in the evening. Adrenalectomy depressed the level of endogenous corticosterone immediately and the growth rate of the liver increased significantly. We were able to prevent this effect by repeated injections of corticosterone at physiological doses. After a 1/3 hepatectomy and a sham-operation, the corticosterone blood level maintained its normal circadian pattern with the exception of a transient increase during the first two post-operative hours. After a hepatectomy of this kind, a negative correlation was found to exist between the adrenal hormone level and the waves of DNA synthesis; the subsequent mitoses appeared in two successive circadian waves of decreasing amplitude, a maximum value being reached in the morning. In rats submitted to a 1/3 hepatectomy and an adrenalectomy simultaneously, the endogenous corticosterone level fell significantly after a post-operative peak. The regenerating pattern was completely different from that induced by 1/3 hepatectomy alone. The rise in the labelling index began earlier and rose to significantly higher values; it was then followed by a single large mitotic wave without any circadian rhythm. These results favour the hypothesis that adrenal hormones have a significant effect on the negative control of liver regeneration. Circadian changes in the corticosterone level were responsible for the nycthemeral pattern observed in the regenerating liver after a partial hepatectomy. The results show a marked inhibition of the G1-S transition, particularly in the evening, when the endogenous corticosterone concentration was at its highest. Also discussed is the relationship between corticoids and 'chalones', which synergetically inhibit the passage from G0 into the cell cycle. [less ▲] Detailed reference viewed: 12 (2 ULg) |
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