Transplacental induction of a specific mutation in fetal Ha-ras and its critical role in post-natal carcinogenesis
✍ Scribed by H. Yamasaki; M. Hollstein; N. Martel; J. R. P. Cabral; D. Galendo; L. Tomatis
- Book ID
- 102865131
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- French
- Weight
- 624 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Mouse skin tumors were produced after transplacental initiation [with 7, I2-dimethylbenz(a)anthracene], only when the skin was treated post-natally with a tumor-promoting agent (12-0-tetradecanoyl phorbol 13-acetate). D N A analysis of tumors showed that all carcinomas analyzed contained a specific mutation (A to T transversion) at the 61st codon of c-Ha-ras.
Fifty per cent of the papillomas analyzed also had this same mutation. The A to T transversion at the 61st codon of Haras was heterozygous in all positive papillomas and carcinomas. No such mutation was found when benzo(a)pyrene was used as an initiating agent. These results indicate that fetal c-Ha-ras can be transplacentally activated through a specific point mutation by a carcinogen, but a cell harboring such a mutation may remain dormant until it encounters a tumorpromoting stimulus.