The effects of N-methyl-N'-nitro-N-nitrosoguanidine on KB cells. I. Growth inhibition and cell killing in relation to inhibition of macromolecular synthesis.
Cytotoxic effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on KB cells were analyzed taking into account cell killing and growth inhibition. Attempts to correlate these effects with macromolecular synthesis inhibition were monitored. At low doses (1 X 10(-6) at 1 X 10(-5) M), MNNG acting for 1 h only inhibited cell proliferation in a dose dependent manner and specifically inhibited DNA synthesis. At intermediate doses (1.6 X 10(-5) at 3.2 X 10(-5) M), treatment resulted in detachment and death of the cells during a 20-h post-incubation period. This effect was related to a dose-dependent inhibition of RNA and protein synthesis. At high doses (greater than 3.2 X 10(-5) M) MNNG treatment resulted in cell killing which was distinct from that produced by lower doses, since the cells did not detach from the glass. At these high doses strong inhibition of RNA and protein synthesis was observed early. When cells prelabelled with radioactive uridine or amino acids were treated with MNNG, the release of labelling into the culture medium increased, especially with uridine prelabelled cells. This increase was very high with the intermediate doses of the drug, but more modest with the strong doses. Furthermore, with the moderate doses, cell size showed greater reduction compared to the control than with the high doses. Thus, cell size reduction and loss of cellular material varied parallel to cell detachment. We hypothesize that moderate doses of MNNG may induce cellular degradation, whereas high doses may prevent it. The significance of this finding is discussed.
D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D046911:Macromolecular Substances; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology* / Q000633:toxicity; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009374:Neoplasms, Experimental / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis
D004273:DNA, Neoplasm; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D008769:Methylnitronitrosoguanidine