Somatic cell genotoxicity at the glycophorin A locus in humans
We have developed an assay for detecting variant erythrocytes that occur as a result of in vivo allele loss at the glycophorin A (GPA) locus on chromosome 4 in humans. This gene codes for an erythroid- specific cell surface glycoprotein, and with our assay we are able to detect rare variant erythrocytes that have lost expression of one of the two GPA alleles. Two distinctly different variant cell types are detected with this assay. One variant cell type (called N{O}) is hemizygous. Our assay also detects homozygous variant erythrocytes that have lost expression of the GPA(M) allele and express the GPA(N) allele at twice the heterozygous level. The results of this assay are an enumeration of the frequency of N{O} and NN variant cell types for each individual analyzed. These variant cell frequencies provide a measure of the amount of somatic cell genotoxicity that has occurred at the GPA locus. Such genotoxicity could be the result of (1) reactions of toxic chemicals to which the individual has been exposed, or (2) high energy radiation effects on erythroid precursor cells, or (3) errors in DNA replication or repair in these cells of the bone marrow. Thus, the GPA-based variant cell frequency can serve as a biodosimeter that indicates the amount of genotoxic exposure each individual has received. Because two very different kinds of variant cells are enumerated, different kinds of genotoxicity should be distinguishable. Results of the GPA somatic genotoxicity assay may also provide valuable information for cancer-risk estimation on each individual. 16 refs.
- Research Organization:
- Lawrence Livermore National Lab., CA (USA)
- Sponsoring Organization:
- DOE/ER; NIOSH
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 6291173
- Report Number(s):
- UCRL-JC-105937; CONF-9010249--4; ON: DE91007129; CNN: CA 48518
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOASSAY
BIOLOGICAL DOSEMETERS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGY
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CELL TRANSFORMATIONS
CHEMOTHERAPY
CHROMOSOMAL ABERRATIONS
DISEASES
DOSEMETERS
ERYTHROCYTES
GENETIC EFFECTS
GENETICS
GLYCOPROTEINS
HEMATOPOIETIC SYSTEM
IN VIVO
MAMMALS
MAN
MATERIALS
MEASURING INSTRUMENTS
MUTAGENS
MUTATIONS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROTEINS
SOMATIC CELLS
THERAPY
TISSUES
TOXICITY
VERTEBRATES