Accumulation of chlorpromazine and thiouracil by human melanoma cells in culture.
The uptake (total radioactivity in intact cells) and incorporation (radioactivity bound to acid-precipitable material) of 14C-chlorpromazine (CPZ) and 14C-thiouracil (TU) were studied using a library of 3 human fibroblast strains and 13 tumour cell lines. In contrast to previous studies using rodent melanomas in vivo, the melanoma lines, including lines with high tyrosinase and melanin contents, did not take up more CPZ and TU than non-melanoma cells (fibroblasts, HeLa cells). Incorporation of CPZ was also broadly similar in all cell types studied. TU was selectively incorporated into the melanoma line having a high tyrosinase and melanin content but not into lines with high tyrosinase activity and low melanin content. While supporting the possibility of selective therapy for heavily-pigmented melanomas using labelled TU derivatives, these results suggest that the action of potentially melanoma-affined compounds should be further evaluated in human cells. Unlabelled CPZ or TU was not selectively toxic to melanoma cells. Unexpectedly, methylation-sensitive tumour cells (Mer-phenotype) were highly resistant to TU, thus providing a new experimental tool for understanding the genesis of this phenotype in vivo.
D002460:Cell Line; D002746:Chlorpromazine / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D008543:Melanins / Q000032:analysis; D008545:Melanoma / Q000032:analysis / Q000201:enzymology / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010670:Phenylthiourea / Q000633:toxicity; D013889:Thiouracil / Q000378:metabolism* / Q000633:toxicity
D008543:Melanins; D013889:Thiouracil; D010670:Phenylthiourea; D014442:Monophenol Monooxygenase; D002746:Chlorpromazine