Multiple oncogene activation in a radiation carcinogenesis model

Conference · Thu Jan 01 04:00:00 EST 1987

OSTI ID:5558776

Garte, S J; Sawey, M J; Burns, F J; Felber, M; Ashkenazi-Kimmel, T

There is evidence from animal systems to suggest that certain oncogenes may be activated by the direct action of the initiating carcinogen. Consistent activation by a point mutation of a single member of the ras oncogene family in different tumors produced by a single agent has been demonstrated. In contrast the c-myc and other oncogenes have been shown to be activated by a process involving chromosomal translocations, enhanced expression, and/or gene amplification. We have examined a panel of 12 late stage rat skin tumors for activation of oncogenes from the ras and myc complementation groups. These tumors were four squamous cell carcinomas, three poorly differentiated carcinomas (clear cell), one each of basal cell carcinoma, sebaceous carcinoma, sarcoma, fibroma, and mixed (largely squamous) histology carcinoma. The positive tumor DNAs were from three poorly differentiated clear cell carcinomas, a sebaceous carcinoma, a squamous cell carcinoma, and a sarcoma. DNA from one of the primary transfectants was positive in a second round of transfection. The transformed phenotype of the transfectants was confirmed by anchorage independent growth and tumorigenicity in nude mice. Southern blot analysis of DNA from primary and secondary transfectants, as well as from nude mouse tumors arising after injection of transfectant cells revealed the presence of rat derived restriction fragments homologous to the K-ras oncogene against the mouse background. Similar experiments using N- and H-ras probes, revealed only the endogenous mouse fragments in transfectant DNA. 11 refs., 1 tab.

• Research Organization: New York Univ., NY (USA). Inst. of Environmental Medicine
• DOE Contract Number: FG02-87ER60539
• OSTI ID: 5558776
• Report Number(s): DOE/ER/60539-2; CONF-870701-12; ON: DE88002636
• Country of Publication: United States
• Language: English

Related Subjects

550400 -- Genetics
560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BODY
DISEASES
GENE AMPLIFICATION
GENES
MAMMALS
NEOPLASMS
ONCOGENES
ORGANS
RADIOINDUCTION
RATS
RODENTS
SKIN
VERTEBRATES