Requirement of long progression time for the expression of neoplastic phenotypes following direct perturbation to specific region(s) of DNA of Syrian hamster embryo cells

Journal Article · Tue Jul 01 04:00:00 EDT 1986 · Cancer Res.; (United States)

OSTI ID:5230668

Tsutsui, T; Ts'o, P O

We have studied the neoplastic transformation of early passage Syrian hamster embryo cells in culture, which were initiated by a specific perturbation of DNA replicated during different periods of S phase. The cells were treated with a 1-h pulse of 5-bromodeoxyuridine (BrdUrd), followed by a 5-min irradiation with near ultraviolet (near UV) light. The treated cells were successively subcultured and tested for growth in soft agar and tumorigenicity in newborn hamsters. Neoplastic transformation was induced by treatment with BrdUrd followed by near UV irradiation within the first 4 h of S phase, which was 5 h in duration. Cells treated with BrdUrd plus near UV irradiation during late S phase (the last hour) or during the absence of DNA synthesis (outside of the S phase) were not transformed. In addition, cultures treated in either G1, G2, or S phase with BrdUrd alone or with near UV alone also were not transformed. While morphological transformation, somatic mutation, and DNA and chromosomal aberrations can be observed either immediately or after a few cell divisions, 100 to 200 population doublings after the treatment were required for the emergence of a neoplastic subpopulation, as measured by anchorage independent growth and tumorigenicity. Furthermore, cellular DNA replicated during the first 4 h of S phase is sensitive to the perturbation which leads to neoplastic transformation. These results indicate that the direct perturbation of specific region(s) of cellular DNA can initiate the neoplastic transformation process; but for full expression of the neoplastic phenotypes, a long progression time is required for the acquisition of anchorage-independent growth and tumorigenicity.

• Research Organization: Nippon Dental Univ., Tokyo, Japan
• OSTI ID: 5230668
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 7; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AZINES
BROMOURACILS
BUDR
CARCINOGENESIS
CELL CULTURES
CELL CYCLE
CELL TRANSFORMATIONS
CHROMOSOMAL ABERRATIONS
DNA
DNA REPLICATION
DRUGS
ELECTROMAGNETIC RADIATION
HAMSTERS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
MAMMALS
MUTATIONS
NEAR ULTRAVIOLET RADIATION
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ONCOGENIC TRANSFORMATIONS
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
PYRIMIDINES
RADIATIONS
RIBOSIDES
RODENTS
ULTRAVIOLET RADIATION
URACILS
VERTEBRATES