Bis-GMAモノマーが培養細胞のコロニー形成とラットの肝機能に及ぼす影響

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The cytotoxic effect of Bis-GMA monomer before and after purification were determined by the colony assay technique using V79 cells. The effects of i.p.administration of purified Bis-GMA monomer on metabolizing enzymes in the rat liver were also investigated. Bis-GMA (Shin Nakamura Chemical Co., Wakayama, Japan) was purified according to the method of Fujisawa et al.(1981). Summary of the study were as follows : (1) Colony assay of V79 cells : V79 cells, seeded at 50 cells/well on a 24-well multiplate were incubated with MEM containing with various concentrations of unpurified or purified Bis-GMA monomer for 6 days. Zinc diethyldithiocarbamate (ZDEC) and zincdibutyldithiocarbamate (ZDBC) were used as standard cytotoxic reference materials. According to the 50% cell inhibitory concentration values (IC_<50>), the cytotoic order of the materials were expressed as ZDEC (0.2 μg/ml) >unpurified Bis-GMA (1.6 μg/ml)> ZDBC (2.8 μg/ml)>purified Bis-GMA (2.9 μg/ml). (2) The effects of Bis-GMA on drug metabolizing enzymes in rat liver : Thirty-six male Wister rats (231±9g) were separated into three experimental groups. Rats of group A (Bis-GMA) were administered purified Bis-GMA, suspended in two parts sterilized olive oil at a dose of 1.0g/kg body weight, once a day on 3 successive days. Group B (Olive oil) rats were similarly treated with olive oil alone for 3 days. Group C rats were untreated as the control. Standard rat chow and tap water were given ad libitum. During the experiment, there were no significant changes in animal body weight between the control and the treated groups. The total amounts of hepatic cytochrome P-450 was four times higher in group A and three times higher in group B than that in group C. On the seventh day, the cytochrome P-450 in the treated groups showed 1.3〜1.5 nmol/mg protein, but this returned to the control level on the fourteenth day. The amount of UDPGT in the treated groups exhibited maximum increases on the seventh day. The concentration of glutathione (GSH) was elevated transiently four days after the last Bis-GMA administration. Then, this activity returned to the control level on the seventh day. GOT and GPT activities in the treated groups were slightly higher than those in the control group on the seventh day of recovery. Alkaline phosphatase and cholinesterase activities in the treated groups were increased on the seventh and fourteenth day, respectively. However, three weeks later, the enzyme activities had returned to the control levels. The i.p.administration of Bis-GMA or olive oil induced elevation of γ-GTP activity throughout the experiment. On the whole, the present findings suggest that Bis-GMA belongs to a group of chemicals which involve glutathione conjugation in the detoxification process. Administration of Bis-GMA resulted in transiently elevated level of drug metabolizing enzymes in rat livers, but these were indistinguishable from elevation induced by administration of olive oil alone.
福岡歯科大学学会の論文
1994-12-31

Bis-GMAモノマーが培養細胞のコロニー形成とラットの肝機能に及ぼす影響

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