Increased H-ras mutation frequency in mammary tumors of rats initiated with N-methyl-N-nitrosourea (MNU) and treated with acrylamide.
We recently demonstrated the incidence and multiplicity of N-methyl-N-nitrosourea (MNU)-induced mammary tumors to be increased by administration of acrylamide (AA) in post-initiation in rats. In the present study, to clarify the mechanisms of enhancement, H-ras gene mutations in mammary tumors induced in MNU-initiated rats with or without subsequent AA administration were investigated. Frequencies of mutations in codon 12 from GGA to GAA were significantly (p < 0.05) higher in rats with AA administration (82%, 23 out of 28 tumors) as compared to those without AA (50%, 9 out of 18 tumors), but the latency and volume of H-ras mutation-harboring tumors were similar to those of the mutation-lacking tumors. No mutations in codons 13 or 61 were detected in either treatment groups. The results thus indicate that H-ras gene mutations in codon 12 play a pivotal role in initiation of carcinogenesis and it appears possible that AA administration may selectively co-stimulate and/or maintain initiated cells via other genomic or non-genomic events in MNU-treated rats.
Cho
Young-Man
YM
Imai
Toshio
T
Hasumura
Mai
M
Watanabe
Naoko
N
Ushijima
Toshikazu
T
Hirose
Masao
M
Nishikawa
Akiyoshi
A
D020106:Acrylamide; D000818:Animals; D003062:Codon / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics*; D008770:Methylnitrosourea; D009154:Mutation; D051381:Rats; D017207:Rats, Sprague-Dawley
D003062:Codon; D020106:Acrylamide; D008770:Methylnitrosourea