End points for biomonitoring: assay sensitivity/selectivity.
Open Access
- 1 May 1996
- journal article
- Published by Environmental Health Perspectives in Environmental Health Perspectives
- Vol. 104 (suppl 3) , 521-525
- https://doi.org/10.1289/ehp.96104s3521
Abstract
Estimation of population exposure and biological impact of potential hazards are central reasons for performing biomonitoring. The sensitivity of the biomonitoring methods and the linkage of the measured phenomenon to human disease are also important, but often overlooked, considerations. We are conducting experiments to evaluate the sensitivity of hprt mutation measurement in the nonhuman primate, the cynomolgus monkey. Our findings demonstrate in the monkey that hypoxanthine guanine phosphoribosyltransferase (hprt) mutations produced in vivo can be detected using technique originally worked out using human cells; cynomolgus monkeys were chosen to avoid many of the complications encountered in studying humans. Sequencing of mutants from the monkey using reverse transcriptase polymerase chain reaction methods has led us to conclude that there is similarity of the spectra observed between the spontaneous mutations detected in the two species. However, more recent data suggest that due to low sensitivity, the method is probably not appropriate for routine biomonitoring of randomly selected populations. For example, the inability of the hprt mutation assay to detect some very potent mutagens in the monkey and the effects of the time-dependent pattern of mutant occurrence serve to urge caution in interpretation of elevation or lack of elevation in mutant frequency. Mechanisms for splitting and archiving samples of human tissues/blood from populations at risk may prove valuable as methods improve.Keywords
This publication has 34 references indexed in Scilit:
- Mutant frequency at the HPRT locus in peripheral blood T-lymphocytes of atomic bomb survivorsMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1995
- Gamma-ray mutagenesis measurement in mammalian cellsMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1995
- Biological effect monitoring in industrial workers following incidental exposure to high concentrations of ethylene oxideMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1995
- DNA sequence analysis of spontaneoushprt mutations arising in vivo in cynomolgus monkey T-lymphocytesEnvironmental and Molecular Mutagenesis, 1995
- Relative sensitivity of the endogenous hprt gene and lacl transgene in ENU‐treated big blue™ B6C3F1 miceEnvironmental and Molecular Mutagenesis, 1995
- Working paper no. 6 Estimation of genetic risks of exposure to chemical mutagens: relevance of data on spontaneous mutations and of experience with ionizing radiationMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1994
- DNA sequence analysis of spontaneous and n‐ethyl‐n‐nitrosourea‐lnduced hprt mutations arising in vivo in cynomolgus monkey t‐lymphocytesEnvironmental and Molecular Mutagenesis, 1992
- Induction of 6‐thioguanine‐resistant lymphocytes in fischer 344 rats following in vivo exposure to n‐ethyl‐n‐nitrosourea and cyclophosphamideEnvironmental and Molecular Mutagenesis, 1991
- Models and assumptions underlying genetic risk assessmentMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1989
- A collaborative exercise on cytogenic dosimetry for simulated whole and partial body accidental irradiationMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1987