Nitric oxide production in endotoxin-resistant C3H/HeJ mice stimulated with flavone-8-acetic acid and xanthenone-4-acetic acid analogues.
The production of nitric oxide in endotoxin-resistant C3H/HeJ mice in response to flavone-8-acetic acid (FAA), derivatives of xanthenone-4-acetic (XAA), endotoxin and recombinant human tumour necrosis factor-alpha (TNF-alpha) was investigated and compared with the induction of haemorrhagic necrosis in subcutaneous M16/C tumours. FAA and XAA analogues stimulated nitric oxide production both in vitro (activated macrophages) and in vivo (plasma nitrate elevation) in both C3H/HeJ and C3H/HeN mice (5,6-dimethyl-XAA greater than 5-methyl-XAA greater than FAA greater than XAA greater than 8-methyl-XAA). Recombinant human TNF-alpha stimulated nitric oxide production equally from both murine strains while endotoxin stimulated nitric oxide production only by C3H/HeN mice. The extent of induction of haemorrhagic necrosis in tumour-bearing mice treated with FAA, 5,6-dimethyl XAA or endotoxin paralleled the effects on nitric oxide production, showing a differential between the two strains of mice only in the case of endotoxin.
Thomsen
L L
LL
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Ching
L M
LM
Joseph
W R
WR
Baguley
B C
BC
Gavin
J B
JB
D000818:Animals; D002478:Cells, Cultured; D004351:Drug Resistance / Q000235:genetics; D004731:Endotoxins / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014966:Xanthenes / Q000494:pharmacology* / Q000627:therapeutic use
D004731:Endotoxins; D005419:Flavonoids; D009566:Nitrates; D014409:Tumor Necrosis Factor-alpha; D014966:Xanthenes; D009569:Nitric Oxide; C066138:xanthenone-4-acetic acid; C049328:flavone acetic acid