TY - JOUR
T1 - Incidence of mutations at codon 61 of the Ha-ras gene in liver tumors of mice genetically susceptible and resistant to hepatocarcinogenesis
AU - Dragani, Tommaso A.
AU - Manenti, Giacomo
AU - Colombo, Bruno M.
AU - Stefania Falvella, F.
AU - Gariboldi, Manuela
AU - Pierotti, Marco A.
AU - Della Porta, Giuseppe
PY - 1991/2
Y1 - 1991/2
N2 - By selective oligonucleotide hybridization of polymerase chain reaction (PCR) amplified tumor DNAs we have analysed the incidence of mutations at codon 61 of the Ha-ras gene in 42 liver tumors spontaneously developed in Balb/c, C3Hf and B6C3 male mice, and in 79 liver tumors induced by the chemical carcinogens diethylnitrosamine (NDEA) and urethan in B6C3 and B6C male and female mice. The incidence of Ha-res gene mutations in both spontaneously developed and urethan-induced liver tumors was 50%-63% in mice genetically susceptible to hepatocarcinogenesis (C3Hf, B6C3) and 7%-9% in mice genetically resistant (Balb/c, B6C). Urethan-induced tumors showed about the same incidence of ras mutations in male and in female B6C3 mice. NDEA-induced tumors showed a low incidence of Ha-ras mutations in both the hybrid mice (3/18 and 1/13 in B6C3 and B6C male mice, respectively). The most frequently found mutations were a C → A transversion at the 1st base of codon 61 in spontaneous tumors, and an A → T transversion at the 2nd base in urethan-induced tumors. Our results indicate that liver tumors induced by NDEA or urethan or spontaneously arisen have a different pattern of Ha-ras mutations at codon 61 and that these mutations constitute a rare molecular alteration in the pathogenesis of liver tumors in genetically resistant mice.
AB - By selective oligonucleotide hybridization of polymerase chain reaction (PCR) amplified tumor DNAs we have analysed the incidence of mutations at codon 61 of the Ha-ras gene in 42 liver tumors spontaneously developed in Balb/c, C3Hf and B6C3 male mice, and in 79 liver tumors induced by the chemical carcinogens diethylnitrosamine (NDEA) and urethan in B6C3 and B6C male and female mice. The incidence of Ha-res gene mutations in both spontaneously developed and urethan-induced liver tumors was 50%-63% in mice genetically susceptible to hepatocarcinogenesis (C3Hf, B6C3) and 7%-9% in mice genetically resistant (Balb/c, B6C). Urethan-induced tumors showed about the same incidence of ras mutations in male and in female B6C3 mice. NDEA-induced tumors showed a low incidence of Ha-ras mutations in both the hybrid mice (3/18 and 1/13 in B6C3 and B6C male mice, respectively). The most frequently found mutations were a C → A transversion at the 1st base of codon 61 in spontaneous tumors, and an A → T transversion at the 2nd base in urethan-induced tumors. Our results indicate that liver tumors induced by NDEA or urethan or spontaneously arisen have a different pattern of Ha-ras mutations at codon 61 and that these mutations constitute a rare molecular alteration in the pathogenesis of liver tumors in genetically resistant mice.
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M3 - Article
C2 - 2000226
AN - SCOPUS:0026100163
VL - 6
SP - 333
EP - 338
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 2
ER -