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H Barbason

Publications and source records attributed to H Barbason.

At least 37 records · Page 2Linked to original sources

Promotion mechanism of phenobarbital and partial hepatectomy in DENA hepatocarcinogenesis cell kinetics effect.

Diethylnitrosamine (DENA, 10 mg kg-1 per day) was fed to rats for 2, 4 and 6 weeks. One week after the cessation of DENA, animals were submitted either to partial hepatectomy or to phenobarbital administration. Partial hepatectomy did not promote neoplastic transformation, except after a 6-week DENA treatment. A minimum of phenobarbital was required to reach a significant promoting effect in DENA carcinogenesis. A too-limited treatment was ineffectual but could be compensated for by prolonged DENA administration. The phenobarbital treatment became unnecessary when neoplastic nodules were present. Phenobarbital continuously given after the carcinogen administration promoted neoplastic transformation even after a subcarcinogenic DENA treatment (2 weeks). It accelerated the pathological evolution and increased the tumour incidence. In these conditions, phenobarbital increased the proliferation advantage of preneoplastic cells over normal cells. In the different experimental modalities, the promoting effect was associated with the induction of chronic cell proliferation, the inhibition of the rapid response to the 2/3 partial hepatectomy and the mitotic circadian rhythm normally present during liver regeneration. It is concluded that the promotion mechanism could consist in disturbing the mitotic control in order to maintain, for a long time, a chronic low level of cell proliferation permitting the selective growth of preneoplastic cells and their subsequent transformation.

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Kinetics of proliferation of rat aortic smooth muscle cells in Goldblatt one-kidney, one-clip hypertension.

Wistar female rats were made hypertensive by applying a silver clip to the left renal artery and removing the right kidney. In aortas, the proliferation fraction of smooth muscle cells, DNA synthesis and wet weight have been correlated with the blood pressure increase subsequent to the operation. A wave of proliferation of smooth muscle cells in the aortic media is triggered immediately after the highest increased rate of blood pressure. When blood pressure stabilizes at high values, the metabolism of nucleic acid within the aortic media resumes its normal level but the arterial changes previously established persist. The sequence of pathological events responsible for these changes could be: increment of blood pressure; increase in wall stress; proliferation of smooth muscle cells; thickening of arterial wall; correction of the wall stress; end of proliferation. The consequence of this early proliferation of aortic smooth muscle cells is not clear but it is probably one of the mechanisms through which high blood pressure is sustained. It can also participate in atherogenesis, being in this way one of the bases of the well-known relationship between hypertension and atherosclerosis.

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Proliferation of preneoplastic lesions after discontinuation of chronic DEN feeding in the development of hepatomas in rat.

Diethylnitrosamine (DEN, 10 mg/kg/day) was fed to rats for 2, 4 and 6 weeks. At different times after feeding with DEN was stopped, growth of preneoplastic lesions has been correlated with pathological evolution (preneoplastic foci, neoplastic nodules and hepatomas). The proliferating fraction in the foci, the cell content, and relative volume of foci increase as a function of the duration of the treatment. The proliferating fraction increases evenly throughout the liver, but, in all experimental modalities, preneoplastic cells show a proliferative advantage over the phenotypically normal tissue. In each experimental group, the proliferative rate correlates with the pathological evolution. After 2 weeks of DEN feeding the growth activity of foci remains very low, and neoplastic nodules are not detectable until the median time of death (14 months). After 4 and 6 weeks, a critical size of the foci is reached, corresponding to the neoplastic transformation, and an increased labelling index is triggered in the lesions and in the phenotypically normal tissue. It is speculated that the "growth pressure" induced by the first carcinogen treatment, associated with the subsequent disturbance of the mitotic control regulation, may be implicated in the process of malignant transformation of preneoplastic lesions.

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Correlation of liver growth and function during liver regeneration and hepatocarcinogenesis.

We have previously studied some parameters of rat liver activity and compared the kinetics of cell proliferation (normal growth or after partial hepatectomy) with some specific hepatic enzymes. The mutually exclusive relationship between division and tissue function, their specific circadian rhythm as well as the "chalone effect" have been used to characterize the normal homeostatic regulatory mechanism in the liver. The same parameters have been recently determined during chemical carcinogenesis. Adult rats, fed long term with diethylnitrosamine (DENA, 10 mg/kg/day) develop liver carcinoma after 90 days of carcinogen administration. The results show that the relationship between the above parameters is progressively disturbed during the second month of treatment. A minimum of 4 weeks of continuous DENA feeding is found to be necessary for the induction of liver cancers. Giving the carcinogen for a second month decreases the delay before death with cancer. Protracting the treatment after the second month has no further effect either on survival or on cancer induction. The mechanism of carcinogenesis is explained by postulating that preneoplastic lesions evolution would closely depend on the homeostatic control disturbances.

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Effects of discontinuation of chronic feeding of diethylnitrosamine on the development of hepatomas in adult rats.

Diethylnitrosamine (DENA) at 10 mg/kg was fed to adult rats either continuously or for periods ranging from 1 to 10 weeks. Survival correlated inversely with the duration of carcinogen feeding. Less than 4 weeks of DENA feeding produced only preneoplastic foci that persisted indefinitely; 4 weeks were found to be necessary for the transformation of preneoplastic lesions into liver cancers; after 6 weeks, the incidence of hepatomas was 100%. The process of liver cancerization appeared to be identical whether DENA was fed for 8 weeks or continuously up to the time of death. These results are discussed in the light of the evolution of the homoeostatic control of liver-cell division during DENA feeding, in order to distinguish the different successive roles played by the carcinogen.

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Long term effects of a single dose of dimethylnitrosamine on the rat liver.

A single injection of DMNA induces in hepatocytes different lesions which are revealed by the mitoses following a partial hepatectomy. The inhibition of mitotic activity, the appearance of micronuclei and the development of hyperplastic nodules were investigated. The results show that the delay between the DMNA treatment and the induction of mitotic activity influences differently the evolution of these changes. The lesions reponsible for the inhibition of mitotic activity and the production of micronuclei are produced when DMNA is given before hepatectomy. They remain unchanged for a long period and are still present five weeks after the injection of the carcinogen. They have disappeared after 10 weeks. On the contrary, the lesions leading to the formation of hyperplastic nodules are at their greatest when DMNA is given at the time of the DNA synthesis following hepatectomy. The data of the present work are compared with previous results obtained by combining X irradiation and hepatectomy.

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Use of synchronization induced by cyclophosphamide in a methylcholanthrene sarcoma with circadian proliferation to rational sequential chemotherapy.

Owing to the circadian activity of tumoral proliferation, cyclophosphamide (CPA) morning injection exerts, on a methylcholanthrene induced sarcoma, a preferential oncostatic effect. This morning injection is followed by a temporary inhibition of mitoses preceding a high mitotic peak, explained by chemo-induced synchronization of tumor cells. Whereas single vinblastine (VLB) administration has no antitumoral effect, an injection of VLB during the described peak is able to improve oncostatic effect of cyclophosphamide. Moreover, the VLB administration at the same moment as CPA suppresses antineoplastic activity of the latter.

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[Kinetic study of the hepatic regeneration in the rat after exeresis of the left lobe only (Hepatectomy of a third of the mass)].

Regeneration is induced after exeresis of the left liver lobe lone (i.e. 1/3 of the normal liver mass). Cell divisions are less numerous than after the usual 2/3 hepatectomy; they appear later and the slope of the first labelling and mitotic indices is much less steep. However, the same circadian rhythm of divisions is also observed and the duration of the cell cycle phases (G2, S and M) are the same whatever the size of the hepatectomy.

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