Somatic mutation and neoplastic transformation induced by (methyl-/sup 3/H)thymidine. [Hamsters]

Journal Article · Thu Apr 01 04:00:00 EST 1982 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3575802· OSTI ID:5458416

Lin, S L; Takii, M; Ts'o, P O.P.

A system for the study of neoplastic transformation as induced by the incorporation of (methyl-/sup 3/H)thymidine is described. Normal diploid golden Syrian hamster embryo fibroblasts were exposed to (methyl-/sup 3/H)thymidine for 17 hr, followed by a brief chase with deoxycytidine- and thymidine-containing growth medium. Analysis of cell curves suggested multihit mechanism with D/sub q/ and D/sub o/ equal to 0.012 and 0.04 ..mu..Ci/ml, respectively. Transformation studies demonstrate that expression of specific neoplastic phenotypes occurs at different post-treatment population doublings (PTPD), beginning with morphological alteration (PTPD 3-4), followed by enhanced fibrinolytic activity (PTPD 11-16) and the ability to clone in both medium containing 1% serum (PTPD 18-32) and soft agar (PTPD 25-32). All treated lines displayed tumorigenicity when examined at PTPD 46, whereas control cultures did not. Two tumor lines obtained from tumor explants were further characterized. Cells treated with equivalent tritium concentrations of (5-/sup 3/H)uridine display neither elevated somatic mutation nor enhanced morphological transformation. DNA damage occurring as a result of (/sup 3/H)thymidine incorporation was shown via mutagenicity studies at loci coding for hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) (HPRT) and the NA/sup +/ /K/sup +/ ATPase (EC 3.6.1.3). (methyl-/sup 3/H)thymidine incorporation resulted in induction of HPRT but not ouabain-resistant mutants. Present studies substantiate the importance of specific DNA/nuclear damage, induced by incorporation of tritiated thymidine, as a cause of neoplastic transformation.

• Research Organization: Johns Hopkins Univ. School of Hygiene and Public Health, Baltimore, MD
• OSTI ID: 5458416
• Journal Information: Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 90:1; ISSN RAREA
• Country of Publication: United States
• Language: English

Related Subjects

560122* -- Radiation Effects on Cells-- Internal Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DECOMPOSITION
DNA
EMBRYOS
FIBRINOLYSIS
FIBROBLASTS
HAMSTERS
HETEROCYCLIC COMPOUNDS
INJURIES
LABELLED COMPOUNDS
MAMMALS
MORPHOLOGICAL CHANGES
MUTATIONS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEOLYSIS
PYRIMIDINES
RADIATION EFFECTS
RADIATION INJURIES
RADIOINDUCTION
RIBOSIDES
RODENTS
SOMATIC CELLS
SOMATIC MUTATIONS
THYMIDINE
TRITIUM COMPOUNDS
VERTEBRATES