The formation and metabolism of N-hydroxymethyl compounds--IV. Cytotoxicity and antitumour activity of N-hydroxymethylformamide, a putative metabolite of N-methylformamide (NSC 3051).
Experiments were conducted to test the hypothesis that N-hydroxymethylformamide (HMF) is the active metabolite of the antitumour agent N-methylformamide (NMF). In an in vitro bioassay against the TLX5 lymphoma HMF was more cytotoxic than NMF; this cytotoxicity was abolished by preincubating the TLX5 cells with semicarbazide, a formaldehyde trapping agent. Similarly, the inhibition of incorporation of radiolabelled thymidine, uridine, formate and leucine into TLX5 cells elicited by HMF was eliminated by preincubation of the cells with semicarbazide. HMF is considerably less toxic to tumour-bearing BDF1 mice than NMF and, unlike NMF, does not reduce hepatic glutathione levels in vivo. HMF has no inhibitory activity against the TLX5 lymphoma or the Sarcoma 180 in mice in vivo and only marginal activity against the M5076 reticulum cell sarcoma; these tumours are highly sensitive to NMF. However, like NMF, HMF inhibits growth of the human mammary tumour MX-1 implanted in the subrenal capsule of mice.
D000818:Animals; D000970:Antineoplastic Agents; D005559:Formamides / Q000494:pharmacology* / Q000633:toxicity; D008099:Liver / Q000187:drug effects; D008223:Lymphoma / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D012513:Sarcoma, Experimental / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005559:Formamides; C002950:methylformamide