RT Journal Article SR Electronic T1 EFFECTS OF HYDROXYCHLOROQUINE ON THE GROWTH OF MAMMALIAN CELLS IN VITRO JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 122 OP 130 VO 141 IS 1 A1 John D. Gabourel YR 1963 UL http://jpet.aspetjournals.org/content/141/1/122.abstract AB The effects of hydroxychloroquine on the growth of several mammalian cell lines have been studied. ML-388 cells were no more sensitive to hydroxychloroquine than were other cell lines tested; all cell lines, including the steroid-resistant ML-388R, required about 1 x 10-5 M hydroxychloroquine for 50% inhibition of growth. In contrast, growth of ML-388 cells was inhibited by concentrations of hydrocortisone more than 3 orders of magnitude lower than required to inhibit growth of L-fibroblasts. Although both hydroxychloroquine and hydrocortisone possess anti-inflammatory activity, the fact that the same concentration of hydroxychloroquine is required to inhibit the steroid sensitive ML-388 cell line as for all other cell lines tested coupled with the lack of cross resistance of the steroid-resistant ML-388R cells to hydroxychloroquine suggests that the two compounds inhibit growth by two different mechanisms. The metabolic effects of hydroxychloroquine were studied in the L-fibroblast. Chemical assay of the cellular constituents of cells grown in the presence and absence of hydroxychloroquine showed that cell division and net DNA synthesis were inhibited at the same time and to about the same extent; DNA per cell was the same in both control and hydroxychloroquine-treated cells. In contrast the accumulation of protein, RNA and acid-soluble amino acids was never depressed as much as cell division leading to increased amounts of these constituents on a per cell basis. Hydroxychloroquine was also shown to inhibit the incorporation of H3-thyrmidine into cold acid-insoluble material at a time when the incorporation of C14-leucine was not yet affected. In addition, hydroxychloroquine was shown to inhibit the incorporation of C14-uridine into DNA and RNA; incorporation into DNA was always inhibited to a greater extent than incorporation into RNA. These data suggest but do not prove a causal relationship between inhibition of DNA synthesis and the inhibition of cell division caused by hydroxychloroquine. Purine and pyrimidine nucleosides added to the growth medium failed to reverse the hydroxychloroquine-induced growth inhibition indicating that the site of block in DNA synthesis probably lies beyond the synthesis of these nucleosides.