In vitro effects of single alkylating agents on normal peripheral blood lymphocytes.
The separate in vitro effects of HN2 and L-PAM on resting and stimulated peripheral blood lymphocytes were evaluated with biochemical and morphologic experimental endpoints. Both alkylating agents caused dose-dependent reduction of protein, RNA, and DNA synthesis, but the patterns of diminution differed. The number of cells staining with Erythrosin B, as a toxicity indicator, also rose with higher drug concentrations, but a large proportion of lymphocytes remained unstained even at the maximum drug dose. Stimulation with PHA partially nullified the suppression caused by HN2 but did not influence the effects of L-PAM. Exposure to PWM rendered the in vitro HN2 innocuous but L-PAM remained cytotoxic. Simultaneous lectin-induced blastogenesis proceeded unaltered. Finally, comparisons between 72 and 4 hr drug exposures imply that interference with intracellular synthesis occurs promptly, continues after drug removal, and is related quantitatively to drug concentration rather than to duration of contact.
D000328:Adult; D002463:Cell Membrane Permeability / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004923:Erythrosine; D005260:Female; D006801:Humans; D037102:Lectins / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008466:Mechlorethamine / Q000494:pharmacology*; D008558:Melphalan / Q000494:pharmacology*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis
D037102:Lectins; D011043:Pokeweed Mitogens; D008466:Mechlorethamine; D012313:RNA; D004247:DNA; D004923:Erythrosine; D008558:Melphalan