The oncogenic action of ionizing radiation on rat skin

Technical Report · Wed Jan 01 04:00:00 EST 1992

DOI:https://doi.org/10.2172/6524809· OSTI ID:6524809

Burns, F J; Garte, S J

The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/[mu]), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of [sup 14]C-thymidine. The return of these cells to S-phase a second time was detected by a second label ([sup 3]H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The [sup 14]C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with [sup 14]C increased after 42 hr and remained relatively constant thereafter.

• Research Organization: New York Univ., NY (United States). Dept. of Environmental Medicine
• Sponsoring Organization: DOE; USDOE, Washington, DC (United States)
• DOE Contract Number: FG02-87ER60539
• OSTI ID: 6524809
• Report Number(s): DOE/ER/60539-11; ON: DE93015580
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ARGON IONS
AZINES
BODY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARCINOGENESIS
CELL TRANSFORMATIONS
CHARGED PARTICLES
DOCUMENT TYPES
ELECTRONS
ELEMENTARY PARTICLES
FERMIONS
GENE AMPLIFICATION
GENES
HETEROCYCLIC COMPOUNDS
IONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEPTONS
MAMMALS
NEON IONS
NUCLEOSIDES
NUCLEOTIDES
ONCOGENES
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PROGRESS REPORT
PYRIMIDINES
RATS
RFLPS
RIBOSIDES
RODENTS
SKIN
SOMATIC CELLS
THYMIDINE
TRACER TECHNIQUES
VERTEBRATES