In an attempt to elucidate the pathological effects of phenobarbital and Vitamin C on dimethylnitro-samine (DMN) or carbon tetrachloride (CC1₄) pretreated DMN induced chronic hepatic lesions, the present study in male Sprague-Dawley rats was undertaken to evaluate the death rate, the number of dysplastic cells, the average nuclear size of dysplastic cells and iron excluded lesions 45, 60 and 75 days after DMN injection. Groups of male rats received a water containing phenobarbital 50mg per 100㎖H₂O or vitamin C 50mg per 100㎖H₂O after intraperitoneal injection of DMN (40mg/kg), or CCI₄(0.4㎖/kg) and DMN (40mg/kg).
For demonstration of iron excluding foci, all animals were iron loaded by subcutaneous injection of 5mg iron dextran/40mg body weight, in the inguinal region, with the sides alternated three times per week for 2 weeks prior to killing.
The results were as follows：
1. The number of liver dysplastic cells increased in the CC1₄ pretreated DMN groups, compared to that of DMN groups. That of the phenobarbital groups was more prominent than that of the Vitamin C groups.
2. There were large and small dysplastic cells. On the 60th day, the large dysplastic cells were relatively prominent, while the small dysplastic cells were prominent on 45th or 75th day. The average dysplastic cell size of the 60th day was much larger than that of the 45th or 75th day.
3. The average nuclear size of dysplastic cells was much larger than that of control. That of dysplastic cells on the 60th day was much larger than that of 45th or 75th day.
4. The liver dysplastic cells in the CC1₄ pretreated DMN groups were noted earlier than those of DMN groups, and the number also increased in the CC1₄ pretreated DMN groups.
5. Mortality in the DMN treated groups was 68.6~74％, while that in the CC1₄ pretreated DMN groups was 71.4-88.6％.
6. Iron exclusion foci were noted at severe dysplastic lesions, while iron was diffusely pigmented in the control.
In summary, the result obtained by the present study indicates dimethylnitrosamine (DMN) induces liver cirrhosis accompanied by liver cell dysplasia.
The degree of liver cell dysplasia increased in the phenobarbital administrated groups or CC1₄ pretreated groups.
We suppose that DMN toxicity was sensitive in the proliferating hepatocytes followed by hepatic toxin administration such as CC1₄ and phenobarbital promoted DMN induced liver cell dysplasia.
We also suppose iron exclusion is a reliable marker for carcinogen induced liver lesions in the rat.
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