Effect of phenobarbital on adult rat liver cells treated with 3?-methyl-4-dimethylaminoazobenzene in primary culture

Miyazaki, Mikihiro; Handa, Yoshihiko; Sato, Jiro

doi:10.1007/bf00399272

Cited by 7 publications

(2 citation statements)

References 12 publications

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“…On the other hand, in the course of our studies on aminoazo dye carcinogenesis of liver cells using primary cultures of adult rat liver cells, we found a very interesting phenomenon that hepatocytes had a prolonged survival rate in the presence of 3 mM phenobarbital, a promoter for hepatocarcinogenesis [20]. After a number of repeated experiments, we confirmed the efficiency of phenobarbital for extending survival of functional hepatocytes from adult rats in primary culture [19].…”

Section: Introductionsupporting

confidence: 57%

Effect of various barbituric acid derivatives on survival of functional hepatocytes from adult rats in primary culture

et al. 1987

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Eighteen barbituric acid (BA) derivatives and three structurally related chemicals (non-BA-derivatives) were tested for their potency in supporting survival of functional hepatocytes from adult rats in primary culture. Of the 18 BA derivatives, nine drugs showed excellent maintenance effect on hepatocyte survival and function. Although four BA derivatives were also effective, their potency was relatively lower. The remaining five BA derivatives and three structurally related chemicals exhibited no maintenance effect. Thus, a correlation was found between the BA derivative structure and the potency for supporting hepatocyte survival in primary culture. The dose response curves of hepatocyte survival were generally biphasic in shape, as a function of BA derivative concentration. The optimum concentrations for observing the morphological and biochemical effects of the BA derivatives differed from each other. The maintenance of hepatocytes was attained only in the continuous presence of the BA derivatives in the medium. The nine excellent BA derivatives efficiently prevented hepatocytes from morphological degeneration which was observed in the control cultures. The surviving hepatocytes in the presence of these BA derivatives showed higher albumin secretion and retained higher basal levels of tyrosine aminotransferase (TAT) activity for at least 2 weeks in primary culture, as compared with control. Furthermore, the addition of dexamethasone (10 microM) caused a 2- to 4-fold induction of TAT activity for at least 2-weeks in primary culture.

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Section: Introductionsupporting

confidence: 57%

Effect of various barbituric acid derivatives on survival of functional hepatocytes from adult rats in primary culture

et al. 1987

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“…12 Thus, the optimal concentration of phenobarbital for in vitro promotion is 1.5 mmol/L. 15 At this concentration, phenobarbital stimulates growth of the initiated cells; after approximately 2 months of treatment they are malignantly transformed and can produce tumours in syngeneic animals. 6 When phenobarbital is absent, the cells fail to be transformed.…”

Section: Phenobarbital Promotion Of Rat Hepatocytes From a Preneoplasmentioning

confidence: 99%

Dose‐dependent biphasic effects of phenobarbital on growth and differentiation of primary culture rat hepatocytes

Miyazaki¹,

Mars²,

Michalopoulos³

et al. 1998

J of Gastro and Hepatol

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The actions of phenobarbital, a liver tumour promoter, on growth and differentiation of primary culture normal rat hepatocytes change biphasically as a function of its concentration. At low concentrations of 0.5-2 mmol/L, phenobarbital enhances DNA synthesis of normal adult rat hepatocytes in the presence of epidermal growth factor (EGF) and/or dexamethasone. This is also true for normal suckling (1-2-week-old) rat hepatocytes, without added growth factor(s), in serum-free primary culture. Contrarily, phenobarbital at high concentrations (3-4 mmol/L) suppresses DNA synthesis of suckling rat hepatocytes. Furthermore, phenobarbital inhibits DNA synthesis of transforming growth factor-a-stimulated primary hepatocytes from normal adult rats in a dose-dependent manner within a concentration range of 3-6 mmol/L. When normal adult rat hepatocytes are led to undergo multiple proliferative cycles upon stimulation with hepatocyte growth factor (HGF) and EGF in the chemically defined hepatocyte growth medium (HGM), 3 mmol/L phenobarbital also remarkably suppresses DNA synthesis. Phenobarbital at 3 mmol/L effectively keeps these hepatocytes morphologically differentiated and accelerates restoration of the expression of markers characteristic of differentiated cells after the initial cellular growth phase. In addition, phenobarbital efficiently supports prolonged survival of the hepatocytes.

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Promotion of 3′‐methyl‐4‐dimethylaminoazobenzene‐initiated adult rat liver cells to malignant state by phenobarbital in culture

Miyazaki

Handa

Suzuki

et al. 1986

Intl Journal of Cancer

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After treatment with 1.5 mM phenobarbital (PB) for about 2 months, non-tumorigenic rat liver epithelial-type cell lines (6F-7 and 6G-5), which were initiated by 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB) in primary culture, showed an increase in plating efficiency, growth in soft agar and production of tumors in syngeneic animals. However, the PB-untreated control cells exhibited neither growth in soft agar nor production of tumors. Gamma-glutamyltranspeptidase (GGT)-positive (6F-7-cl-7) and negative (6F-7-cl-8) colonial clones, which were derived from 6F-7 cells, were also treated with 1.5 mM PB for about 2 months. The growth of GGT-positive 6F-7-cl-7 cells was not suppressed but rather stimulated by PB at 1.5 mM, whereas that of GGT-negative 6F-7-cl-8 cells was severely inhibited. Furthermore, the PB-treated 6F-7-cl-7 cells produced tumors in syngeneic animals, but the PB-treated 6F-7-cl-8 cells produced no tumors. The spontaneous cell line 6A-6, which was derived from the 3'-Me-DAB-untreated primary liver cell culture and was GGT-negative, did not exhibit tumorigenicity after treatment with 1.5 mM PB for the same period of time as described above. In conclusion, PB treatment efficiently and rapidly promoted the 3'-Me-DAB-initiated cells to a malignant state.

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Effect of phenobarbital on adult rat liver cells treated with 3?-methyl-4-dimethylaminoazobenzene in primary culture

Cited by 7 publications

References 12 publications

Effect of various barbituric acid derivatives on survival of functional hepatocytes from adult rats in primary culture

Effect of various barbituric acid derivatives on survival of functional hepatocytes from adult rats in primary culture

Dose‐dependent biphasic effects of phenobarbital on growth and differentiation of primary culture rat hepatocytes

Promotion of 3′‐methyl‐4‐dimethylaminoazobenzene‐initiated adult rat liver cells to malignant state by phenobarbital in culture

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