p53 mutations in early neoplastic lesions of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.
Rat experimental models using N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as an initiating agent have been widely used to study carcinogenic processes in the urinary bladder. In this study, early neoplastic lesions from 10 male F344 rats treated with 0.05% BBN for 16 weeks were analyzed for changes in the H-ras or p53 genes by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing. Lesions were pooled for each of the 10 rats and six showed point mutations in the p53 gene and one in the H-ras gene. These results would indicate that BBN-induced rat urinary bladder carcinomas are similar to human urinary bladder carcinomas with respect to alterations in the p53 and H-ras genes and that p53 gene alterations are relatively early events in rat urinary bladder carcinogenesis induced by BBN treatment.
First Department of Pathology, Nagoya City University Medical School, Japan.
T
T
Masui
I
I
Don
N
N
Takada
K
K
Ogawa
T
T
Shirai
S
S
Fukushima
D000818:Animals; D001483:Base Sequence; D002085:Butylhydroxybutylnitrosamine; D005091:Exons; D016158:Genes, p53; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D011916:Rats, Inbred F344; D001743:Urinary Bladder / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000235:genetics*
D002085:Butylhydroxybutylnitrosamine