title: Cellular cadmium responses in subpopulations T20 and T27 of human lung carcinoma A549 cells.
abstract: Subpopulations T20 and T27, cloned from the human lung carcinoma line A549, differ significantly in their Cd2+ cytotoxic response. T27 has an LC50 of 31 microM Cd2+ and a cytotoxic response threshold of 5 microM Cd2+, whereas the T20s LC50 is 15 microM Cd2+ and there is no observed threshold for cytotoxicity. Cadmium-induced metallothionein (MT) synthesis, cadmium accumulation, glutathione (GSH) content, and Cd2(+)-induced changes in GSH content were studied in T20 and T27 in an attempt to determine the mechanism(s) causing differential cytotoxic response. MT synthesis measured by following Cd2(+)-induced [35S] incorporation into MT was found not to differ between T20 and T27. There is, however, a difference in Cd2+ accumulation between the two subclones. T20 and T27 cells were exposed to 5 microM Cd2+ for different times or to different concentrations of Cd2+ for 8 h. The T27 subline, which is the more Cd2+ resistant, was found to accumulate significantly more Cd2(+)-both as a function of time exposed to Cd2+ and as a function of Cd2+ concentration. The two subpopulations were found to have comparable initial GSH contents, but showed different Cd2(+)-induced changes in [GSH] when the cells were exposed to 5 microM Cd2+. T27 cells maintained their GSH content following Cd2+ exposure but T20 cells showed a Cd2(+)-induced decrease in GSH content. The results indicate that the difference in Cd2+ cytotoxic response between A549--T20 and A549--T27 cells is not attributable to alterations in MT synthesis nor to a difference in initial GSH content. Relative Cd2+ cytotoxicity also does not in these cells correlate with relative Cd2+ accumulation. The fact that T27 cells accumulate more Cd2+ and yet are more Cd2+ resistant than T20 cells suggests that T27 cells have a much more effective non-MT mechanism to handle intracellular Cd2+. This may involve different GSH metabolism and/or yet undefined molecular factors.
authors.affiliation: Department of Zoology, Iowa State University Ames 50011.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Kang
authors.forename: S T
authors.initials: ST
authors.lastname: Nuutero
authors.forename: J A
authors.initials: JA
authors.lastname: Clapper
authors.forename: P
authors.initials: P
authors.lastname: Jenkins
authors.forename: M D
authors.initials: MD
authors.lastname: Enger
mesh_terms: D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D003553:Cystine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms; D008668:Metallothionein / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D014410:Tumor Stem Cell Assay
chemical_list: D002104:Cadmium; D003553:Cystine; D008668:Metallothionein; D005978:Glutathione