Inhibition of beta-propiolactone-induced neoplasia of the forestomach and large bowel by 4-mercaptobenzene sulfonate in mice and rats.
Studies have been initiated to find compounds that can trap direct-acting carcinogens within the lumen of the gastrointestinal tract and thus prevent these carcinogens from attacking tissues of the host. Sodium 4-mercaptobenzene sulfonate (4-MBSNa) is a potent nucleophile and was found to react rapidly in vitro with the direct-acting carcinogen beta-propiolactone (BPL). In further investigations 4-MBSNa was shown to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA-100 to BPL and a second direct-acting carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine. Subsequent experiments were performed to determine if 4-MBSNa would inhibit BPL-induced carcinogenesis in vivo. In the first of these, 4-MBSNa was administered by p.o. intubation to female A/J mice 5 min before p.o. administration of BPL. Under these conditions inhibition of carcinogenesis of the forestomach occurred. In a second experiment, 4-MBSNa was given by rectal intubation 5 min before BPL also administered intrarectally. Administration of BPL intrarectally produced adenomatous polyps of the large intestine. The occurrence of these neoplasms was inhibited by the prior administration of 4-MBSNa. The data presented show that 4-MBSNa has the capacity to trap direct-acting carcinogens and to inhibit the occurrence of BPL-induced neoplasia.
Hochalter
J B
JB
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
Wattenberg
L W
LW
Coccia
J B
JB
Galbraith
A R
AR
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D007783:Lactones / Q000633:toxicity*; D008297:Male; D008769:Methylnitronitrosoguanidine; D051379:Mice; D011420:Propiolactone / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
D001557:Benzenesulfonates; D007783:Lactones; D008769:Methylnitronitrosoguanidine; D011420:Propiolactone; C055719:4-mercaptobenzenesulfonic acid