ras gene alterations in invasive and non-invasive rat bladder carcinomas induced by N-methyl-N-nitrosourea.
We have established a reliable method to induce invasive and non-invasive carcinomas in the heterotopically transplanted urinary bladder of rats by repeated injection of N-methyl-N-nitrosourea (MNU), and examined the alterations of the ras oncogenes and ras oncogene product (p21) in the induced tumours. The incidence of muscle-invasive carcinomas was proportional to the total dose of MNU. When 5, 6 or 12 doses of MNU were used, muscle invasive carcinomas developed in 22, 58 or 45% of animals, respectively, after a mean observation period, respectively, of 54 +/- 9, 45 +/- 13 and 38 +/- 3 weeks. Whereas activated H-ras gene was detected in only one non-invasive carcinoma by DNA transfection assay, seven of 18 non-invasive and invasive carcinomas showed activated ras p21 when examined by immunoblot analysis. Amplification or rearrangement of myc or epidermal growth factor (EGF) receptor gene was not observed. The results indicate that alterations of ras gene may be involved in the development of rat bladder carcinomas but not of invasiveness.
Yura
Y
Y
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611.
Azuma
M
M
Uchida
K
K
Momose
H
H
Oyasu
R
R
D000818:Animals; D015139:Blotting, Southern; D002277:Carcinoma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D008297:Male; D008770:Methylnitrosourea; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009693:Nucleic Acid Hybridization; D015689:Oncogene Protein p21(ras) / Q000032:analysis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm; D008770:Methylnitrosourea; D015689:Oncogene Protein p21(ras)