[Effects of mesalazine on liver carcinogenesis in medium-term bioassay using rats].
A two stage carcinogenesis promotion test using phenobarbital (PB) as a positive control was performed on mesalazine in rats (F344,male). Pathological and immunohistological examinations were performed to examine the cell damage and proliferation in the liver and kidneys. As the initiation treatment, groups 1,2,3 and 5 were administered 300 mg/kg diethylnitrosamine (DEN)dissolved in 0.9% physiological saline, and group 4 was administered 5 ml/kg 0.9% physiological saline once intraperitoneally. Then group 1 was orally administered a water solution (5 ml/kg) containing 0.5% CMC-Na, and groups 2,3 and 4 similar water solution but containing 150, 300 and 300 mg/kg mesalazine, respectively. Group 5 was administered 0.05% PB mixed in feed from weeks 2 to 8. Partial (2/3) hepatectomy was performed in all 5 groups at week 3 after DEN administration. NO clear differences between the groups were observed in general conditions, body weight or amount of food consumption. The number or area-size of hepatic GST-P positive altered cell foci revealed no significant differences between groups 1,2 and 3, but a significant increase in number and area-size was observed in group 5. No GST-P positive cell foci were detected in group 4. The number of altered cell foci (H.E. staining) in the DENgroups administered mesalazine was the same as that in group 1. Thus, mesalazine did not promote hepatocarcinogenesis in the present experimental system. Statistically insignificant appearances of basophilic and acidophilic changes were observed in the renal tubular epithelium and mineral deposits in the renal papillary region and cortical margin region. The PCNA labeling rate was significantly lower in group 4, corresponding with the histological finding showing no proliferation of the renal tubular epithelium. Judging from the above test results, mesalazine was likely to show neither a promotion effect on the initiation induced by DEN nor cell proliferative activity on the kidneys by administration for this experimental period.
Biosafety Research Center, Foods, Drugs and Pesticides (An-Pyo Center), Shizuoka, Japan.
Y
Y
Hirouchi
S
S
Kakamu
A
A
Shoji
K
K
Kobayashi
M
M
Enomoto
S
S
Hatakeyama
K
K
Yonezawa
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests / Q000379:methods; D004435:Eating / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine