Tissue-specific activating mutations of Ha- and Ki-ras oncogenes in skin, lung, and liver tumors induced in mice following transplacental exposure to DMBA
| Autor: | J. Ricardo P. Cabral, D. Galendo, Lorenzo Tomatis, Nicole Martel, Alexandre Loktionov, Monica Hollstein, Hiroshi Yamasaki |
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| Rok vydání: | 1990 |
| Předmět: |
Cancer Research
Lung Neoplasms Skin Neoplasms Liver tumor 9 10-Dimethyl-1 2-benzanthracene DMBA Biology medicine.disease_cause Mice Liver Neoplasms Experimental Pregnancy medicine Animals Codon Transversion Molecular Biology Mutation Transition (genetics) Oncogene Transplacental medicine.disease Fetal Diseases Genes ras Organ Specificity Immunology Cancer research Female Carcinogenesis Polymorphism Restriction Fragment Length |
| Zdroj: | Molecular Carcinogenesis. 3:134-140 |
| ISSN: | 1098-2744 0899-1987 |
| DOI: | 10.1002/mc.2940030306 |
| Popis: | Transplacental carcinogenesis represents a good model in which to study the involvement of tissue-specific oncogene activation in carcinogenesis because a single exposure to a carcinogen induces tumors at various sites. We tested tumors of the skin, liver, and lung produced in mice after transplacental 7,12-dimethylbenz[a]-anthracene (DMBA) exposure for possible activation of ras genes. XbaI restriction fragment-length polymorphism analysis has shown that exposure to DMBA in utero may result in appearance of A----T transversion at the second position of codon 61 of Ha-ras oncogene in skin and liver tumors but not in lung tumors. Moreover, DNA samples isolated from spontaneous and DMBA-induced lung and liver tumors were analyzed for mutations at the same position of Ki-ras oncogene using differential hybridization with specific oligonucleotides. Among five spontaneous lung tumors, three cases of A----G transition, and one case of A----T transversion were found, whereas four of ten lung tumors of DMBA-treated animals were positive for A----T mutation. No Ki-ras mutation was detected in one spontaneous and four DMBA-induced hepatomas. In two cases, we revealed Ki-ras A----T mutation in the lung tumor and Ha-ras mutation in the liver tumor taken from the same animal. These results indicate first that DMBA treatment may induce A----T mutation at the second position of codon 61 both in Ha-ras and in Ki-ras and, second, that the role of different activated oncogenes in carcinogenesis may differ, depending on the tissue in which the tumor develops. |
| Databáze: | OpenAIRE |
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