The development of in vitro mutagenicity testing systems using T-lymphocytes: Research progress report: June 1, 1988--May 31, 1989

Technical Report · Mon May 01 04:00:00 EDT 1989

DOI:https://doi.org/10.2172/6098183· OSTI ID:6098183

Albertini, R. J.

We will summarize our refinement of the methodology for cloning human T-lymphocytes and quantifying in vivo T-cell mutant frequencies at the hprt locus. The ability to maintain in vitro proliferation of these cells allows molecular characterizations, including analyses of hprt outlined elsewhere, the latter permits definitions of mutation frequencies which underlie the measured mutant frequencies. This unique aspect of the T-lymphocyte cloning assay is extremely important because it permits quantitation of in vivo mutational events, which are the events of public health interest. An increase in in vivo mutational events is only one of the causes of increased mutant frequencies, the other is in vivo clonal expansions of mutant cells. Clonal expansions have an importance of their own, but the implications are different than for increases in mutations. Several examples of in vivo clonal expansions will de detailed. The ability to maintain in vitro proliferation of T-cell colonies also allows molecular analyses of the mutations in the hprt gene. The results of both southern blot analyses for gene deletions and rearrangements and direct sequencing for smaller changes such as base substitutions will be given. A spectrum of hprt mutations is being developed both for unexposed, ''normal'' humans as well as for humans exposed to ionizing irradiation in the course of radioimmunoglobulin therapy (RIT) for hepatoma treatment. 11 figs., 4 tabs.

• Research Organization: Vermont Univ., Burlington (USA)
• DOE Contract Number: FG02-87ER60502
• OSTI ID: 6098183
• Report Number(s): DOE/ER/60502-03; ON: DE89013800
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIGENS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CLONING
CONNECTIVE TISSUE CELLS
DESIGN
DNA HYBRIDIZATION
DNA-CLONING
DOCUMENT TYPES
DOSES
ELECTROMAGNETIC RADIATION
ELECTROPHORESIS
GAMMA RADIATION
GENE MUTATIONS
HISTOCOMPATIBILITY COMPLEX
HYBRIDIZATION
IONIZING RADIATIONS
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
MUTAGEN SCREENING
MUTATION FREQUENCY
MUTATIONS
ORGANIC COMPOUNDS
PRIMATES
PROGRESS REPORT
PROTEINS
RADIATION DOSES
RADIATIONS
RADIOSENSITIVITY
RECEPTORS
SCREENING
SOMATIC CELLS
VERTEBRATES