TY - JOUR
AU - Gupta, Radhey, S.
AB - Abstract Toxicities of various microtubule inhibitors, namely, colchicine, podophyllotoxin, maytansine, vinblastine, nocodazole, griseofulvin, and steganacine, toward numerous independently established cell lines from three different species, namely, human, mouse, and Chinese hamster, were examined. Some of these inhibitors (namely, colchicine, vinblastine, taxol, and maytansine) were found to exhibit large (between tenfold and fiftyfold) differences in their toxic and antimitotic concentrations toward various cell lines and these differences appeared to be species related inasmuch as all cell lines from a particular species showed similar sensitivities toward these inhibitors. Of the three species examined, cells of human origin exhibited maximum sensitivity toward these inhibitors while Chinese hamster cells were found to be most resistant. The reduced cellular transport of [3H]colchicine and [3H]vinblastine in Chinese hamster cells as compared to the cellular transport in human cells and the equivalent binding of [3H]col-chicine and [3H]vinblastine to microtubule proteins in cell extracts from both these lines provided strong evidence that the observed differences in toxicity to these inhibitors were most likely caused by differences in the cellular transport of these drugs. In contrast to the toxicities of the above compounds, the toxicities of other microtubule inhibitors such as podophyllotoxin, steganacine, griseofulvin, and nocodazole were found to be very similar for cells from all three species, indicating that the cellular transport of these 2 groups of microtubule inhibitors differed in some important respect. Some implications of the observed species-specific differences in drug toxicity to clinical studies are discussed. 2 Supported by research grants from the Medical Research Council and the National Cancer Institute of Canada. This content is only available as a PDF. Author notes 3 Department of Biochemistry, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. 4 I thank Rajni Gupta and Dawn Kirkconnell for technical assistance and Barbara Sweet for typing the manuscript.
TI - Species-Specific Differences in Toxicity of Antimitotic Agents Toward Cultured Mammalian Cells
JF - JNCI: Journal of the National Cancer Institute
DO - 10.1093/jnci/74.1.159
DA - 1985-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/species-specific-differences-in-toxicity-of-antimitotic-agents-toward-P8sQKgfDG3
SP - 159
EP - 164
VL - 74
IS - 1
DP - DeepDyve
ER -