Role of oncogene activation during prenatal (transplacental) initiation and postnatal promotion of mouse skin tumours.
The transplacental initiation-postnatal promotion model of mouse skin carcinogenesis is useful in studying the molecular and cellular mechanisms of perinatal carcinogenesis. Offspring transplacentally exposed to an initiating dose of a carcinogen typically do not produce any skin tumours in the absence of postnatal treatment; many skin tumours appear only when they are treated with tumour-promoting agents postnatally. Tumour-promoting agents alone produce no skin tumours or only a few. Thus, two stages of carcinogenesis, initiation and promotion, can be conveniently separated. Our results indicate that fetal c-Ha-ras can be transplacentally activated through a specific point mutation by a carcinogen. However, since postnatal promotion was essential for the production of tumours, they also suggest that a cell harbouring such a mutation may remain dormant until it encounters a tumour-promoting stimulus. Since a higher fraction of carcinomas than papillomas contained the specific mutation in Ha-ras, it is postulated that those papillomas with the point mutation have a selective advantage to progress towards carcinomas.
Yamasaki
H
H
International Agency for Research on Cancer Lyon, France.
Hollstein
M
M
Cabral
J R
JR
Tomatis
L
L
D000818:Animals; D000831:Animals, Newborn; D002273:Carcinogens / Q000494:pharmacology; D003043:Cocarcinogenesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000187:drug effects; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011519:Proto-Oncogenes / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics*
D002273:Carcinogens