| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1986: ¥1,000,000 (Direct Cost: ¥1,000,000)
|
|---|
| Research Abstract |
Using a human ovarian cancer cell line of germ cell origin (JOHYL-1), Adriamycin(ADM)-, Cisplatinum(CDDP)-, Carboquon(CQ)- and Vincristine (VCR)- resistant cells were produced by culturing the cells with these anticancer drugs at 10^<-6> mu/ml initially, with the concentration boing then increased stepwise by 10^<-1> mug/ml up to 10^<-2> mug/ml for CQ, ADM and VCR and 10^<-1> mug/ml for CDDP. Each of the resistant cells population thus obtained were examined for their biological properties.
1) The drug-resistant cells, when exposed in culture to respective drugs for 72 hours, gave IC_<50> (mug/ml) of 3.2 x 10^<-3> for CQ, 5.8 x10^<-2> for ADM, 1.1 x 10^<-1> for VCR and 2.5 for CDDP, thus being thought to 28-78 times more resistant than JOHYL-1 cells.
2) The doubling time was 38 hes for CQ-resistant cells, 58 hrs for ADM-resistant cells, 31 hrs for VCR-resistant cells and 30 hrs for CDDP-resistant cells, thus being definitely longer than the corresponding value for JOHYL-1.
3) Study of DNA histograms suggested that CDDP-resistant cells are provided with a DNA damage-respairing mechanism.
4) Study of cross resistance to other anticancer drugs showed that CDDP-resistant cells to ADM and ADR-resistant cells to CDDP were no evidence of acquired cross resistance.
5) CDDP-resistant cells were measured serially for the doubling time, IC_<50> (mug/ml) and resistance ratio and also determined for changes in these parameter after being implanted in nude mice. The obtained results were 26 hrs, 4.4 x 10^<-1> and 14, respectively. It became thus obvious that the drug resistance of CDDP-resistant cells were greatly diminished in biologic property is currently being investigated.
|
