Response of a high-glucuronidase human tumour xenograft to aniline mustard.
The HT29R colonic adenocarcinoma xenograft has been shown to be rich in the enzyme beta-glucuronidase. Experiments in rodent systems have demonstrated a marked anti-tumour effect of the drug aniline mustard (AM) on tumours with high levels of this enzyme (e.g. the plasmacytomas PC5 and PC6). We have found that AM is no more effective than its analogue paramethyl aniline mustard (PMAM) or other alkylating agents against the HT29R xenograft. Amongst the possible explanations for this may be: (1) The wide shoulder on the cell-survival curve shown for exposure to alkylating agents of HT29R in vivo. (2) Lack of correlation between physiological availability of beta-glucuronidase and the high levels measured by the standard assay. (3) Increased beta-glucuronidase levels in host mouse marrow, making the latter potentially more susceptible to AM damage.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology; D000816:Aniline Mustard / Q000627:therapeutic use*; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D009588:Nitrogen Mustard Compounds; D000816:Aniline Mustard; D005966:Glucuronidase