Multiple endpoints for somatic mutations in humans provide complementary views for biodosimetry, genotoxicity and health risks.
While monitoring people with multi-endpoint analysis is only just beginning, the indications of complementarity of these assays are already evident. Since two different tissue types are analyzed, effects of uneven exposure or tissue-specific sensitivities or development kinetics and persistence of each cell type can be addressed. The differing analytical techniques in determining variant cells lead to particular advantages for each assay procedure. The GPA assay can be performed rather quickly on small blood volumes (as little as 0.1 ml). A similar potential exists for the Hb assay, although sophisticated instrumentation development is still required to make this assay easily performable. Both the HPRT and HLA assays require long term tissue growth and many-fold larger (10-30 ml) blood samples. However, both the HPRT and HLA assays have the advantage that they select variant cells that contain nuclei, so that detailed characterization of their mutagenesis is possible using Southern blots, hybridization analysis, and gene sequencing. Since erythrocytes have no nucleic acids, so these effects cannot be measured using the GPA or Hb assay. Other differences between the assays are the target size, chromosomal location, and control signals. Each gene locus is on a different chromosome, with GPA, HLA and Hb genes on autosomes and HPRT on the X chromosome. The target size for GPA and HPRT are about 40kb, whereas HLA A locus is 5kb and the Hb target is one base. These differences should result in much different sensitivity to different mutagenic phenomena, such as radiation effects or different chemical effects. The multiple differences between assays that are designed to detect similar kinds of events occurring in vivo in humans leads us to conclude that all these assays could well be performed on the same blood samples, and the information gained would be much more than the separate assays could yield. Biodosimetry and estimation of cancer initiation could become realistic goals instead of simply significant desires.
Jensen
R H
RH
Biomedical Sciences, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Bigbee
W L
WL
Langlois
R G
RG
D000375:Aging / Q000235:genetics; D004781:Environmental Exposure; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D009153:Mutagens; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D011839:Radiation, Ionizing; D012307:Risk Factors; D013577:Syndrome
D009153:Mutagens