The development of in vitro mutagenicity testing systems using T-lymphocytes
During the past four months we have continued our study of in vitro induction of mutations in human T-lymphocytes and molecular characterization of these induced mutations. Our primary effort has involved determination of the size of deletion events involving the hprt gene. We have analyzed 57 mutants for codeletion of 20 different Xq26 region anonymous DNA probes. We have now ordered the five probes which show codeletion in some mutants, relative to the hprt gene. We are now investigating the physical size of these deletions by us of pulsed field electrophoresis. We have also studied a unique type of deletion mutation found in cord blood samples. This mutation involves a specific deletions of exons 2 and 3, with breakpoints at identical sites in introns 1 and 3. Thirteen mutants from 10 newborns have been shown to have characteristics consistent with a V(D)J recombinase mediated mutational event. As part of our study of the induction of mutations by in vitro exposure to gamma irradiation, we have investigated the effect of inhibiting DNA repair by use of incubation in cytosine arabinoside/release with deoxycytidine. We have also continued our study of in vivo mutation frequencies in humans exposed to ionizing irradiation in the course of radioimmunoglobulin therapy (RIT) for cancer. The mutant frequencies are elevated in the post-RIT patients and 40% of the mutations involve deletions/rearrangements of the hprt gene with total gene deletions predominating (17.6% of the mutations). The fraction of mutants with these structural alterations correlated with the cumulative amount of radioactivity received, providing a possible indicator of total in vivo chronic exposure to ionizing irradiation.
- Research Organization:
- Vermont Univ., Burlington, VT (USA)
- Sponsoring Organization:
- DOE; USDOE, Washington, DC (USA)
- DOE Contract Number:
- FG02-87ER60502
- OSTI ID:
- 5625685
- Report Number(s):
- DOE/ER/60502-5; ON: DE91012283
- Country of Publication:
- United States
- Language:
- English
Similar Records
The development of in vitro mutagenicity testing systems using T-lymphocytes: Research progress report: June 1, 1988--May 31, 1989
The development of in vitro mutagenicity testing systems using T-lymphocytes: Progress report, November 1, 1987--May 31, 1988
Related Subjects
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DNA REPAIR
DOCUMENT TYPES
ELECTROMAGNETIC RADIATION
ELECTROPHORESIS
GAMMA RADIATION
GENE MUTATIONS
IMMUNOLOGY
IMMUNOTHERAPY
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 131
IODINE ISOTOPES
IONIZING RADIATIONS
ISOTOPES
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MEDICINE
MUTAGENESIS
MUTATIONS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
PRIMATES
PROGRESS REPORT
RADIATION EFFECTS
RADIATIONS
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOINDUCTION
RADIOISOTOPES
RADIOLOGY
RADIOSENSITIVITY
RADIOTHERAPY
RECOVERY
REPAIR
SOMATIC CELLS
THERAPY
VERTEBRATES