Use of cytogenetic endpoints in human lymphocytes as indicators of exposure to genotoxicants.
Toxicity Testing. New Approaches and Applications in Human Risk Assessment. Li AP, ed., New York: Raven Press, 1985 Jan; :41-50
The utility of the human lymphocyte assay for population monitoring of genotoxicant exposure is reviewed. For studies of chromosome type aberration (CTA), peripheral lymphocytes are cultured in the presence of bromodeoxyuridine (BrdU), stained with Giemsa, and analyzed in their first metaphase after mitogenic stimulation. For analysis of sister chromatid exchange (SCE), it is necessary to analyze cells in mitotic division after stimulation and growth in the presence of BrdU. CTAs are formed during or after DNA replication in G1 stage, and chromatid type aberrations are formed during or after DNA replication in the S-stage or G2 stage. Following irradiation, CTAs are produced in non cycling G0 stage of the cell cycle. The frequency of aberrations is proportional to the dose in-vivo and in-vitro. During chronic exposures, the aberration frequency reaches an equilibrium where new aberrations are formed and some existing ones lost from the sampled population. Since some lymphocytes survive more than 20 years and aberration frequency declines exponentially, an approximate estimate of received dose can be made. CTA induced by chemicals are produced during S-phase; therefore, all aberrations are of the chromatid type. An increase in CTA indicates an exposure has occurred, but no exposure level can be estimated. SCE frequency can be increased over background level by a wide range of chemical agents, in many cases at a lower concentration than that required for CTA. No adverse health effects are associated with increase in SCE at this time. There is insufficient information on the relationship between SCE frequency and exposure level. When irradiated or chemically treated cells are incubated with cytosine-arabinoside, an increase in the sensitivity to aberrations occurs. The frequency of SCE increases five times when chlorodeoxyuridine is used instead of BrdU. The author concludes that it is premature to predict the usefulness of the lymphocyte assay for determining the degree of genetic and/or somatic risks after chemical exposures.
NIOSH-Grant; Deoxyribonucleic-acids; Chromosome-damage; Radiation-exposure; Blood-cells; Screening-methods; Toxic-materials; Cell-alteration; Exposure-levels
Book or book chapter
Toxicity Testing. New Approaches and Applications in Human Risk Assessment
Radiology University of Iowa 14 Medical Laboratories Iowa City, Iowa 52242