Carcinostatic activity of methylglyoxal and related substances in tumour-bearing mice.

摘要: Methylglyoxal treatment of tumour cells in vitro primarily depresses protein synthesis, contrast to trans-4-hydroxypent-2-enal (HPE) which preferentially inhibits DNA synthesis. and hpe are potent carcinostatic agents but relatively ineffective vivo. Both aldehydes have a short half-life vivo may explain their poor properties when administered other than peritumorally. Several possibilities increasing the effective were investigated including (i) multiple intraperitoneal injections, (ii) concomitant administration an inhibitor glyoxalase I, (iii) aldehyde-cysteine adducts, (iv continuous intravenous infusion. (36 mg/kg i.p., twice daily) was slightly less inhibiting growth solid form Ehrlich carcinoma dose 72 (inj. 1); 36 2) 46.2% compared 51%. The aldehyde more aginst ascitic tumour, with 99.76% inhibition after giving daily for five days followed by days. I S-(p-bromobenzyl)-glutathione didnot significantly enhance activity methylglyoxal against tumour. Nicotinamide (1% w/v drink) similarily inactive. combination nicotinamide effect (P 0.05) alone mg/kg, Methylglyoxal-N-acetyl-L-cysteine four times toxic methylglyoxalalone marginally Doses these adducts equivalent 144 per day P optimal regime (67.5% 51%). Treatment mice bearing Sarcoma 180 doses (i.p.) HPE-cysteine adduct HPE 32-256 increased survival time comparison controls. 2-3 effective, dose-for-dose, growth. Purified buffered has LD50 on infusion into right lateral tail vein 3.0 mg/g (seven at 2.8 ml/day). Local oedema necrosis occurs excess 0.25-0.5 forms syngeneic tumours: squamous D; lymphosarcoma 1 (WH/Ht mice); spontaneous mammary D5056 (CBA/CA mice). A maximum volume delay 3.4 Day 17 0.001) transplantation observed 0.5 Days 11-17 CBA/CA D40 Tumour regrowth termination therapy eliminated significant difference between control methylglyoxal-treated tumours 27. (0...