Twenty-six-week carcinogenicity study of sulfamethoxazole in CB6F1-Tg-rasH2 mice.
Sulfamethoxazole (SMX), a hormone-mediated rodent-specific nongenotoxic carcinogen, was administered to CB6F1 mice carrying a human prototype c-Ha-ras gene (Tg-rasH2) at doses of 0, 25, 100 or 400 mg/kg/day and to the wild-type mice at a dose of 400 mg/kg/day in feed for 26 weeks to evaluate the carcinogenicity and to validate the Tg-rasH2 model. N-Methyl-N-nitrosourea was administered at an intraperitoneal dose of 75 mg/kg to Tg-rasH2 as a positive control and the experimental system was confirmed to be valid. Histopathological examination revealed adenomas of the lung and Harderian gland and hemangiosarcoma of the spleen at low frequencies in the Tg-rasH2 treated with SMX; however, no statistically significant differences were observed either in the onset or prevalence rates of these neoplasms compared with that in the control group. Between the wild-type mice and Tg-rasH2, the onset rate and prevalence of the neoplasms were not significantly different, but the neoplasms tended to be more frequent in Tg-rasH2 mice showing a sensitivity to tumorigenicity. Follicular epithelial cell hyperplasia was observed in the thyroid gland in the groups of Tg-rasH2 given 100 mg/kg SMX or more, but no neoplastic lesion was observed. SMX was judged to be negative for carcinogenic potential in Tg-rasH2 in the present study.
Torii
M
M
Developmental Research Laboratories Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Itoh
F
F
Yabuuchi
K
K
Ohno
K
K
Kominami
G
G
Hirano
K
K
Tasaki
T
T
Nara
H
H
D000818:Animals; D001835:Body Weight; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D011905:Genes, ras; D006243:Harderian Gland / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D013160:Splenic Neoplasms / Q000473:pathology; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000633:toxicity*; D013961:Thyroid Gland / Q000473:pathology
D002273:Carcinogens; D008770:Methylnitrosourea; D013420:Sulfamethoxazole