Temporal order of replication of genes responsible for hypoxanthine phosphoribosyl transferase and Na/sup +//K/sup +/ ATPase in chemically transformed human fibroblasts

Journal Article · Sun Jun 01 04:00:00 EDT 1986 · J. Cell. Physiol.; (United States)

DOI:https://doi.org/10.1002/jcp.1041270316· OSTI ID:5327462

Tsutsui, T; Suzuki, N; Elmore, E; Maizumi, H

The cytotoxic and mutagenic effects of a direct perturbation of DNA during various portions of the DNA synthetic period (S phase) of a chemically induced, transformed line (Hut-11A cells) derived from diploid human skin fibroblasts were examined. The cells were synchronized by a period of growth in low serum with a subsequent blockage of the cells at the G1/S boundary by hydroxyurea. This method resulted in over 90% synchrony, although approximately 20% of the cells were noncycling. Synchronized cells were treated for each of four 2-h periods during the S phase with 5-bromodeoxyuridine (BrdU) followed by irradiation with near-ultraviolet (UV). The BrdU-plus-irradiation treatment was cytotoxic and mutagenic, while treatment with BrdU alone or irradiation alone was neither cytotoxic nor mutagenic. The cytotoxicity was dependent upon the periods of S phase during which treatment was administered. The highest lethality was observed for treatment in early to middle S phase, particularly in the first 2 h of S phase, whereas scare lethality was observed in late S phase. The BrdU-plus-irradiation treatment induced ouabain- and 6-thioguanine-resistant mutants, while BrdU alone or irradiation alone was not mutagenic. Ouabain-resistant mutants were induced during early S phase by the BrdU-plus-irradiation treatment. 6-Thioguanine-resistant mutants, however, were induced during middle to late S phase. These results suggest that a certain region or regions in the DNA of Hut-11A cells, as designated by their specific temporal relationship in the S phase, may be more sensitive to the DNA perturbation by BrdU treatment plus near-UV irradiation for cell survival and that gene(s) responsible for Na/sup +//K/sup +/ ATPase is replicated during early S phase and gene(s) for hypoxanthine phosphoribosyl transferase is replicated during middle to late S phase.

• Research Organization: Nippon Dental Univ. Tokyo, Japan
• OSTI ID: 5327462
• Journal Information: J. Cell. Physiol.; (United States), Journal Name: J. Cell. Physiol.; (United States) Vol. 3; ISSN JCLLA
• Country of Publication: United States
• Language: English

Related Subjects

560110* -- Radiation Effects on Biochemicals-- (-1987)
560301 -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACID ANHYDRASES
AMIDES
ANIMAL CELLS
ANTIMETABOLITES
ATP-ASE
AZINES
BIOLOGICAL EFFECTS
BROMOURACILS
BUDR
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CULTURES
CELL CYCLE
CONNECTIVE TISSUE CELLS
DNA REPLICATION
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
FIBROBLASTS
GENETIC EFFECTS
GLYCOSIDES
GLYCOSYL TRANSFERASES
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
HYDROXYUREA
HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE
MUTAGENESIS
NEAR ULTRAVIOLET RADIATION
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OUABAIN
PENTOSYL TRANSFERASES
PHOSPHOHYDROLASES
PYRIMIDINES
RADIATIONS
RIBOSIDES
SOMATIC CELLS
STROPHANTHINS
SYNCHRONOUS CULTURES
SYNERGISM
TOXICITY
TRANSFERASES
ULTRAVIOLET RADIATION
URACILS