HUMAN-CHROMOSOME-3 MEDIATES GROWTH ARREST AND SUPPRESSION OF APOPTOSIS IN MICROCELL HYBRIDS

Chemotherapeutic treatment of tumor cells leads either to tumor cell d eath (usually by apoptosis) or to the formation of drug-resistant subp opulations. Known mechanisms of cancer cell drug resistance include ge ne amplification and increased expression of drug transporters. On the other hand, normal cells survive many forms of chemotherapy with mini mal damage probably because of their capacity for growth arrest and st ringent control of apoptosis. Microcell hybrids between B78 (murine me lanoma) and HSF5 (normal human fibroblasts) were analyzed to identify a new human chromosomal region involved in the promotion of drug-induc ed growth arrest and suppression of apoptosis. In these hybrids, the p resence of human chromosome 3 was strongly associated with suppression of apoptosis via G(1) and G(2) growth arrest during exposure to the a ntimetabolite N-phosphonoacetyl-L-aspartate (PALA), suggesting that a gene(s) on chromosome 3 serves an antiproliferative role in a drug-res ponsive growth arrest pathway.