Induction of sister chromatid exchanges and inhibition of cellular proliferation in vitro. I. Caffeine
While many agents have been examined for their ability to induce SCE's, complete dose-response information has often been lacking. We have reexamined the ability of one such compound - caffeine - to induce SCEs and also to inhibit cellular proliferation in human peripheral lymphocytes in vitro. An acute exposure to caffeine prior to the DNA synthetic period did not affect either SCE frequency or the rate of cellular proliferation. Chronic exposure to caffeine throughout the culture period lead to both a dose-dependent increase in SCEs (SCE/sub d/ or doubling dose = 2.4 mM; SCE/sub 10/ or the dose capable of inducing 10 SCE = 1.4 mM) and a dose-dependent inhibition of cellular proliferation (IC/sub 50/ or the 50% inhibition concentration = 2.6 mM). The relative proportion of first generation metaphase cells, an assessment of proliferative inhibiton, increased linearly with increasing caffeine concentrations. However, SCE frequency increased nonlinearly over the same range of caffeine concentrations. Examination of the ratio of nonsymmetrical to symmetrical SCEs in third generation metaphase cells indicated that caffeine induced SCEs in equal frequency in each of three successive generations. The dependency of SCE induction and cellular proliferative inhibition on caffeine's presence during the DNA synthetic period suggests that caffeine may act as an antimetabolite in normal human cells.
- Research Organization:
- Univ. of Pennsylvania, Philadelphia
- OSTI ID:
- 6304772
- Journal Information:
- Environ. Mutagen.; (United States), Vol. 4
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CAFFEINE
GENETIC EFFECTS
TOXICITY
CELL PROLIFERATION
INHIBITION
BIOASSAY
CHROMATIDS
SISTER CHROMATID EXCHANGES
ANALEPTICS
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
CENTRAL NERVOUS SYSTEM AGENTS
CHROMOSOMAL ABERRATIONS
DRUGS
HETEROCYCLIC COMPOUNDS
MUTATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PURINES
XANTHINES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)