End points for biomonitoring: assay sensitivity/selectivity.
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.
Aaron
C S
CS
Upjohn Company, Kalamazoo, Michigan 49007, USA. saaron@pwinet.upj.com
Zimmer
D M
DM
Harbach
P R
PR
Yu
R L
RL
D000818:Animals; D000080890:Duocarmycins; D004784:Environmental Monitoring / Q000379:methods; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005038:Ethylnitrosourea / Q000633:toxicity; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007211:Indoles; D007933:Leucomycins / Q000633:toxicity; D008252:Macaca fascicularis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D012680:Sensitivity and Specificity; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects
D000080890:Duocarmycins; D007211:Indoles; D007933:Leucomycins; D009153:Mutagens; C018782:CC 1065; D005020:Ethyl Methanesulfonate; D007041:Hypoxanthine Phosphoribosyltransferase; D005038:Ethylnitrosourea