Point mutation in codons 12 and 61 of the ha‐ras gene in rat urinary bladder carcinomas induced by N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide

T. Masui, A. M. Mann, E. M. Garland, T. Okamura, P. L. Johansson, Samuel Monroe Cohen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Male F344 rats were fed N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide (FANFT) for up to 4 wk, then were given the basal diets (Prolab 3200 or AIN‐76A) with or without 5% sodium saccharin for up to 100 wk. Eleven transitional cell carcinomas (TCCs), one undifferentiated carcinoma, and two sarcomas of the urinary bladder were examined for the expression of ras gene product, p21, by immunohistochemical staining and western blot analysis. Point mutation in codons 12 or 61 of the Ha‐ras genes amplified by polymerase chain reaction was examined by a slot‐blot screening procedure using allele‐specific oligonucleotide probes. Immunohistochemical staining showed enhanced immunoreactivity with the antibody to ras p21 in seven TCCs and one undifferentiated carcinoma. Western blot analysis showed faster migration of the p21 band in 6 of 11 TCCs. Oligonucleotide hybridization revealed the point mutation in codon 12 of Ha‐ras gene (GGA → GTA in 1 TCC) and in codon 61 (CAA → CGA in 5 TCCs and CAA → CTA in 1 TCC). Two mutations in codons 12 and 61 coexisted in one tumor, which were found to be present in different Ha‐ras alleles. The incidence of Ha‐ras gene mutations were similar in groups treated with (3 of 6) or without (3 of 8) sodium saccharin. These results suggest the involvement of activated Ha‐ras gene in rat urinary bladder carcinogenesis induced by FANFT.

Original languageEnglish (US)
Pages (from-to)210-215
Number of pages6
JournalMolecular Carcinogenesis
Volume3
Issue number4
DOIs
StatePublished - 1990

Fingerprint

Transitional Cell Carcinoma
Point Mutation
Codon
Urinary Bladder
Carcinoma
FANFT
Genes
Saccharin
Western Blotting
Staining and Labeling
Proto-Oncogene Proteins p21(ras)
ras Proteins
Mutation
Oligonucleotide Probes
Inbred F344 Rats
Oligonucleotides
Sarcoma
formamide
Carcinogenesis
Alleles

Keywords

  • Ha‐ras
  • Rat urinary bladder carcinogenesis
  • oncogene

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Point mutation in codons 12 and 61 of the ha‐ras gene in rat urinary bladder carcinomas induced by N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide. / Masui, T.; Mann, A. M.; Garland, E. M.; Okamura, T.; Johansson, P. L.; Cohen, Samuel Monroe.

In: Molecular Carcinogenesis, Vol. 3, No. 4, 1990, p. 210-215.

Research output: Contribution to journalArticle

@article{5cb17558e7e640e4927f50212c741227,
title = "Point mutation in codons 12 and 61 of the ha‐ras gene in rat urinary bladder carcinomas induced by N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide",
abstract = "Male F344 rats were fed N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide (FANFT) for up to 4 wk, then were given the basal diets (Prolab 3200 or AIN‐76A) with or without 5{\%} sodium saccharin for up to 100 wk. Eleven transitional cell carcinomas (TCCs), one undifferentiated carcinoma, and two sarcomas of the urinary bladder were examined for the expression of ras gene product, p21, by immunohistochemical staining and western blot analysis. Point mutation in codons 12 or 61 of the Ha‐ras genes amplified by polymerase chain reaction was examined by a slot‐blot screening procedure using allele‐specific oligonucleotide probes. Immunohistochemical staining showed enhanced immunoreactivity with the antibody to ras p21 in seven TCCs and one undifferentiated carcinoma. Western blot analysis showed faster migration of the p21 band in 6 of 11 TCCs. Oligonucleotide hybridization revealed the point mutation in codon 12 of Ha‐ras gene (GGA → GTA in 1 TCC) and in codon 61 (CAA → CGA in 5 TCCs and CAA → CTA in 1 TCC). Two mutations in codons 12 and 61 coexisted in one tumor, which were found to be present in different Ha‐ras alleles. The incidence of Ha‐ras gene mutations were similar in groups treated with (3 of 6) or without (3 of 8) sodium saccharin. These results suggest the involvement of activated Ha‐ras gene in rat urinary bladder carcinogenesis induced by FANFT.",
keywords = "Ha‐ras, Rat urinary bladder carcinogenesis, oncogene",
author = "T. Masui and Mann, {A. M.} and Garland, {E. M.} and T. Okamura and Johansson, {P. L.} and Cohen, {Samuel Monroe}",
year = "1990",
doi = "10.1002/mc.2940030408",
language = "English (US)",
volume = "3",
pages = "210--215",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Point mutation in codons 12 and 61 of the ha‐ras gene in rat urinary bladder carcinomas induced by N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide

AU - Masui, T.

AU - Mann, A. M.

AU - Garland, E. M.

AU - Okamura, T.

AU - Johansson, P. L.

AU - Cohen, Samuel Monroe

PY - 1990

Y1 - 1990

N2 - Male F344 rats were fed N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide (FANFT) for up to 4 wk, then were given the basal diets (Prolab 3200 or AIN‐76A) with or without 5% sodium saccharin for up to 100 wk. Eleven transitional cell carcinomas (TCCs), one undifferentiated carcinoma, and two sarcomas of the urinary bladder were examined for the expression of ras gene product, p21, by immunohistochemical staining and western blot analysis. Point mutation in codons 12 or 61 of the Ha‐ras genes amplified by polymerase chain reaction was examined by a slot‐blot screening procedure using allele‐specific oligonucleotide probes. Immunohistochemical staining showed enhanced immunoreactivity with the antibody to ras p21 in seven TCCs and one undifferentiated carcinoma. Western blot analysis showed faster migration of the p21 band in 6 of 11 TCCs. Oligonucleotide hybridization revealed the point mutation in codon 12 of Ha‐ras gene (GGA → GTA in 1 TCC) and in codon 61 (CAA → CGA in 5 TCCs and CAA → CTA in 1 TCC). Two mutations in codons 12 and 61 coexisted in one tumor, which were found to be present in different Ha‐ras alleles. The incidence of Ha‐ras gene mutations were similar in groups treated with (3 of 6) or without (3 of 8) sodium saccharin. These results suggest the involvement of activated Ha‐ras gene in rat urinary bladder carcinogenesis induced by FANFT.

AB - Male F344 rats were fed N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide (FANFT) for up to 4 wk, then were given the basal diets (Prolab 3200 or AIN‐76A) with or without 5% sodium saccharin for up to 100 wk. Eleven transitional cell carcinomas (TCCs), one undifferentiated carcinoma, and two sarcomas of the urinary bladder were examined for the expression of ras gene product, p21, by immunohistochemical staining and western blot analysis. Point mutation in codons 12 or 61 of the Ha‐ras genes amplified by polymerase chain reaction was examined by a slot‐blot screening procedure using allele‐specific oligonucleotide probes. Immunohistochemical staining showed enhanced immunoreactivity with the antibody to ras p21 in seven TCCs and one undifferentiated carcinoma. Western blot analysis showed faster migration of the p21 band in 6 of 11 TCCs. Oligonucleotide hybridization revealed the point mutation in codon 12 of Ha‐ras gene (GGA → GTA in 1 TCC) and in codon 61 (CAA → CGA in 5 TCCs and CAA → CTA in 1 TCC). Two mutations in codons 12 and 61 coexisted in one tumor, which were found to be present in different Ha‐ras alleles. The incidence of Ha‐ras gene mutations were similar in groups treated with (3 of 6) or without (3 of 8) sodium saccharin. These results suggest the involvement of activated Ha‐ras gene in rat urinary bladder carcinogenesis induced by FANFT.

KW - Ha‐ras

KW - Rat urinary bladder carcinogenesis

KW - oncogene

UR - http://www.scopus.com/inward/record.url?scp=0025049290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025049290&partnerID=8YFLogxK

U2 - 10.1002/mc.2940030408

DO - 10.1002/mc.2940030408

M3 - Article

C2 - 2206284

AN - SCOPUS:0025049290

VL - 3

SP - 210

EP - 215

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

SN - 0899-1987

IS - 4

ER -