CAFFEINE ENHANCED MEASUREMENT OF MUTAGENESIS BY LOW-LEVELS OF GAMMA-IRRADIATION IN HUMAN-LYMPHOCYTES

The well-known action of caffeine in synergizing mutagenesis (includin g chromosome aberrations) of agents like ionizing radiation by inhibit ion of cellular repair processes has been incorporated into a rapid pr ocedure for detection of mutagenicity with high sensitivity. Effects o f 5-10 rads of gamma-irradiation, which approximate the human lifetime dose accumulation from background radiation can be detected in a two- day procedure using an immortalized human WBC culture. Chromosomally v isible lesions are scored on cells incubated for 2 h after irradiation in the presence and absence of 1.0 mg/ml of caffeine. An eightfold am plification of scorable lesions is achieved over the action of radiati on alone. This approach provides a closer approximation to absolute mu tagenicity unmitigated by repair processes, which can vary in differen t situations. It is proposed that mutagenesis testing of this kind, us ing caffeine or other repair-inhibitory agents, be employed to identif y mutagens in their effective concentrations to which human population s may be exposed; to detect agents such as caffeine that may synergize mutagenic actions and pose epidemiologic threats; and to discover eff ective anti-mutagens. Information derived from the use of such procedu res may help prevent cancer and newly acquired genetic disease.