Paraquat is not accumulated in B16 tumor cells by the polyamine transport system.
We have examined the effect of difluoromethylornithine on the ability of B16 melanoma cells to take up putrescine and the 4,4'-dipyridyl herbicide paraquat. Pretreatment with difluoromethylornithine for 24 hr enhanced putrescine uptake by inducing the maximum capacity of the transport system without affecting the Km for the substrate. Paraquat uptake was minor compared with that of putrescine and was not affected by difluoromethylornithine. Neither putrescine, spermidine or spermine at concentrations up to 100 microM inhibited the accumulation of paraquat. However, paraquat competitively inhibited putrescine transport (Ki = 54 +/- 10 microM). Exposure of the B16 melanoma cells for 24 hr to increasing concentrations of paraquat produced a dose-dependent inhibition of DNA synthesis. Difluoromethylornithine pretreatment did not affect paraquat toxicity. These data show that paraquat is not taken up into B16 melanoma cells by the uptake system responsible for transporting putrescine. Moreover, it is likely that the difluoromethylornithine inducible polyamine transport system in B16 melanoma cells is characteristically different to that previously described in normal mammalian lung since the latter is reportedly capable of transporting both putrescine and paraquat.
Minchin
R F
RF
Department of Pharmacology, University of Western Australia, Nedlands.
Martin
R L
RL
Ilett
K F
KF
D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology; D007700:Kinetics; D008546:Melanoma, Experimental / Q000378:metabolism*; D010269:Paraquat / Q000378:metabolism* / Q000633:toxicity; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism*; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D011073:Polyamines; D013096:Spermine; D010269:Paraquat; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine