Activation of ras oncogenes and expression of tumor-specific transplantation antigens in methylcholanthrene-induced murine fibrosarcomas.
The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3-methylcholanthrene (3-MCA), was tested in NIH 3T3 transformation assay. Activation of K-ras and N-ras was found in 7 and 3 cases respectively. No H-ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K-ras mutation at codon 12, 3 at codon 13 and 1 at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N-ras were also found, one of which was simultaneous with a K12 mutation. Tumor-specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA+ tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3-MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of the 6 TSTA- tumors showed ras mutation. The results suggest that 3-MCA-induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K- and N- but not H-ras gene and that such mutation is accompanied by the expression of TSTA.
Carbone
G
G
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Borrello
M G
MG
Molla
A
A
Rizzetti
M G
MG
Pierotti
M A
MA
Della Porta
G
G
Parmiani
G
G
D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis*; D001483:Base Sequence; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D011905:Genes, ras; D006649:Histocompatibility Antigens / Q000032:analysis*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D014162:Transfection
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen; D008748:Methylcholanthrene