Effects of barbital on neuro-oncogenesis in a transplacental carcinogenicity model using F344 rats.
Effects of barbital (BB) on neuro-oncogenesis were examined in a rat transplacental carcinogenesis model. Pregnant F344 rats were divided into 7 groups. Dams in group I received subcutaneous injections of 10 mg/rat 1-butyl-1-nitrosourea (BNU) on the days 15, 18 and 21 of pregnancy and dams in groups II-IV, 1mg/rat BNU on the same time schedule. In addition to the treatment with BNU, dams in group IV were given 0.125% BB solution as their drinking water from the day 12 of pregnancy to parturition. Offspring in groups III and IV received 0.125% BB solution as drinking water from 4 weeks of age until the termination of the study. Animals in groups V and VI were given 0.25% and 0.125% BB solutions, respectively, in the peri- and postnatal period without BNU treatment. Dams in group VII received 250 mg/kg BB subcutaneously on the days 15, 18 and 21 of pregnancy. Offspring in all groups were observed until 105-116 weeks of age. High yields of neurogenic tumors, such as gliomas and neurinomas, were observed in group I. In groups II, III and IV, single cases of a chordoma, a granular cell tumor, and a neurinoma and a malignant reticulosis, which are known to occur spontaneously, were noted, although no gliomas were found. No neurogenic tumors were observed in groups V-VII. With regard to lesions other than those in neurogenic organs, a significant increase in liver tumors was observed in group III compared to group II. In contrast, lung tumors were not found in group III, while they were observed in groups II and IV. These results suggest that BB has no neuro-carcinogenic activity in the rat transplacental carcinogenesis model.
Tanigawa
H
H
Division of Safety Assessment, Roussel Morishita Co., Ltd., Shiga, Japan.
Onodera
H
H
Maekawa
A
A
D000818:Animals; D001462:Barbital / Q000633:toxicity*; D001932:Brain Neoplasms / Q000139:chemically induced*; D015197:Carcinogenicity Tests; D002817:Chordoma / Q000139:chemically induced; D005260:Female; D005910:Glioma / Q000139:chemically induced; D016586:Granular Cell Tumor / Q000139:chemically induced; D016399:Lymphoma, T-Cell / Q000139:chemically induced; D008297:Male; D009369:Neoplasms / Q000139:chemically induced; D009442:Neurilemmoma / Q000139:chemically induced; D017599:Neuroectodermal Tumors / Q000139:chemically induced* / Q000473:pathology; D009607:Nitrosourea Compounds / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011916:Rats, Inbred F344
D009607:Nitrosourea Compounds; D001462:Barbital; C002738:N-nitrosobutylurea