Specific patterns of oncogene activation in transplacentally induced tumors

Journal Article · Mon Jan 01 04:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.2.718· OSTI ID:6710289

Sukumar, S ^[1]; Barbacid, M ^[2]

---

1. Salk Institute of Biological Studies, La Jolla, CA (USA)
2. Squibb Institute for Medical Research, Princeton, NJ (USA)

Transplacental exposure of rats to a single dose of the direct acting carcinogen methylnitrosourea (MNU) results in the induction of a variety of neoplasias of neuroectodermal, epithelial, and mesenchymal origin. Molecular analysis of the oncogenes present in these tumors revealed a striking degree of tissue specificity. New oncogenes were found to be reproducibly activated in tumors derived from the peripheral nervous system (PNS), but not in those arising from the central nervous system (CNS). No ras oncogenes were found in either PNS- or CNS-derived tumors. However, Ha-ras oncogenes were detected in each of three mammary carcinomas and Ki-ras oncogenes were present in each of five kidney mesenchymal tumors. These results illustrate that phenotypic expression of activated oncogenes in vivo is not a random process and suggest that normal developmental programs may play an important role in modulating the activation of specific oncogenes by chemical carcinogens. PCR analysis revealed that each of the ras oncogenes detected in these transplacentally induced tumors became activated by the same G {yields} A transition in the second base of codon 12. Since G {yields} A transitions are the preferred mutations induced by MNU, it is likely that these ras oncogenes may have been directly targeted by MNU during embryonic development.

• OSTI ID: 6710289
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:2; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOLOGICAL EFFECTS
CARBONIC ACID DERIVATIVES
CARCINOMAS
CHEMICAL ACTIVATION
DISEASES
DNA BASE TRANSITIONS
FETAL MEMBRANES
GENE AMPLIFICATION
GENE MUTATIONS
GENES
MAMMALS
MEMBRANES
METHYL NITROSOUREA
MUTAGENS
MUTATIONS
NEOPLASMS
NITROSO COMPOUNDS
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOTYPE
PLACENTA
PRENATAL EXPOSURE
RATS
RODENTS
VERTEBRATES