TECHNOLOGY FOR IMPROVING IN VITRO MAMMALIAN CELL CULTURE AND

OUR PROPOSED RESEARCH AND DEVELOPMENT IS DIRECTED TOWARD A SIGNIFICANTLY IMPROVED IN VITRO MAMMALIAN CELL CULTURE. THIS RESEARCH IS MOTIVATED BY THE POTENTIAL BENEFIT OF BEING ABLE TO CARRY OUT AUTOMATED IN VITRO GENETIC TOXICOLOGY ASSAYS WITH SIGNIFICANTLY REDUCED TIMES AND COSTS. OUR NEW TECHNOLOGY AIMS TO USE LARGE NUMBERS (E.G., 109 CELLS) WITH INSTRUMENTATION BASED ON OPTICAL MEASUREMENTS AND RAPID COMPUTER DETERMINATIONS. OUR OVERALL STRATEGY IS TO DEVELOP BOTH IN VITRO MAMMALIAN CELL CULTURE TECHNIQUES AND RELATED INSTRUMENTATION, SO THAT MANY MAMMALIAN TOXICOLOGY ASSAYS DEVELOPED BY OTHERS CAN BE CARRIED OUT MORE RAPIDLY AND WITH LESS EXPENSE. THE KEY IS THE ABILITY TO QUANTITATE SMALL NUMBERS (E.G., 100 TO 1,000) OF MUTANT CELLS OUT OF AN INITIAL POPULATION OF 109 MAMMALIAN CELLS, AND TO DO THIS WITHIN A FEW DAYS. FOR MAMMALIAN CELLS WHICH HAVE A TYPICAL DIVISION TIME OF 1 DAY, THIS MIGHT TRANSLATE INTO A TECHNOLOGY WHICH CAN DETECT SMALL NUMBERS OF MICROCLONES (2 TO 32 CELLS) OF MAMMALIAN CELLS. AS IN VITRO MAMMALIAN CELL GENETOX ASSAYS BECOME MORE WIDELY ESTABLISHED, SUCH A TECHNOLOGY SHOULD HAVE WIDESPREAD APPLICATION IN DEALING WITH THE CHEMICAL TESTING REQUIREMENTS NOW BELIEVED DESIRABLE OR NECESSARY.