Differential effects of abrin on normal and tumor cells.
The effects of the plant toxin abrin on normal mouse embryonic fibroblasts (MEF), an untransformed mouse cell line (NIH 3T3), and two mouse tumor cell lines (LMTK- and S-180) were studied. Measurements of cell growth and colony formation showed that MEF and S-180 cells were more sensitive to abrin intoxication than NIH 3T3 and LMTK- cells. Also, the effects of abrin on the inhibition of [3H]leucine and [3H]thymidine incorporation were more evident in MEF and S-180 cells. The basis for these varying responses to abrin by the four different cells was examined. The number of abrin binding sites per cell was determined from [125I]abrin binding studies: NIH 3T3 and LMTK- cells had significantly fewer abrin binding sites than MEF and S-180 cells. The fate of the [125I]abrin after internalization was examined by gel electrophoresis and autoradiography. A pattern of time-dependent degradation was observed, degradation being more rapid in NIH 3T3 and S-180 cells than in LMTK- and MEF cells. We conclude that the varying responses of different cells to the toxin abrin may be due to several factors, including the relative number of abrin binding sites on the cell surface and the rate of degradation of the toxin once internalized. The results also show that the sensitivities of the cells to abrin do not necessarily correlate with their normal or neoplastic state.
D000036:Abrin / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002999:Clone Cells / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004705:Endocytosis; D005690:Galactose / Q000494:pharmacology; D007928:Lethal Dose 50; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009374:Neoplasms, Experimental / Q000473:pathology*; D010940:Plant Proteins / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011975:Receptors, Mitogen / Q000378:metabolism; D012510:Sarcoma 180 / Q000473:pathology
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010940:Plant Proteins; D011975:Receptors, Mitogen; C035488:abrin receptor; D000036:Abrin; D004247:DNA; D005690:Galactose