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Neoplastic transformation of golden Syrian hamster embryo cells by /sup 3/H thymidine exposure

Thesis/Dissertation ·
OSTI ID:6145636
Incorporation of (methyl-/sup 3/H)thymidine, to cause specific nuclear/DNA damage, induces somatic mutation and neoplastic transformation. Normal diploid golden Syrian hamster embryo (GSHE) fibroblasts were exposed to (methyl-/sup 3/H)thymidine for 17 h, followed by a brief chase with deoxycytidine- and thymidine-containing growth medium. Analysis of cell killing curves suggested a multihit mechanism with D/sub q/ and D/sub 0/ equal to 0.01 ..mu..Ci/ml and 0.04 ..mu..Ci/ml respectively. Transformation studies demonstrate that expression of specific neoplastic phenotypes occurs at different post-treatment population doublings (PTPDs) beginning with morphological alteration (PTPD 3-4), followed by enhanced fibrinolytic activity (PTPD 11-16) and abilities to clone in 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. Incorporation of identical tritium doses using (5./sup 3/H) uridine did not significantly enhance somatic mutation or induce morphological transformation. It is concluded that the neoplastic transformation of GSHE fibroblasts by /sup 3/H-thymidine results specifically from DNA damage and that the transformation process reflects a gradual, rather than sudden, loss of growth control.
OSTI ID:
6145636
Country of Publication:
United States
Language:
English