The colonic bacteria produce large quantities of hydrogen sulfide (H 2 S) and methanethiol (CH 3 SH), highly toxic compounds with LD 50 's for rodents that are on the same order of magnitude as cyanide. Given the very high exposure of the colonic mucosa to H 2 S and CH 3 SH, local tissue damage would be expected if the mucosa did not possess an efficient detoxification mechanism. The possibility that sulfide might be injurious to colonic mucosa was first proposed by Roediger and Nance (1), who postulated that excess sulfide production could play an etiological role in ulcerative colitis.A variety of high-molecular-weight thiols are detoxified in a methylation reaction catalyzed by thiol S-methyltransferase (2-4). Recent literature assumes that a similar mechanism is used in the detoxification of the lowmolecular-weight thiols H 2 S and CH 3 SH (5-8). Such methylation would result in the conversion of H 2 S to CH 3 SH, and then CH 3 SH to dimethylsulfide (CH 3 SCH 3 ), a relatively nontoxic compound. However, the reported rate of methylation of H 2 S by rat colonic mucosa is only about 10 -13 mol/min per milligram of protein (8). This activity appears to be many orders of magnitude less than that required to metabolize H 2 S released in the colon, which we found to occur at a rate of about 10 -7 mol/min in the rat cecum (9).In the process of incubating H 2 S and CH 3 SH with rat cecal mucosa, we observed that both gases disappeared far more rapidly than could be accounted for by reported methylation rates. The present report describes in vitro and in vivo experiments demonstrating that the colonic mucosa possesses a very efficient, but largely unrecognized, system to metabolize H 2 S and CH 3 SH. This system proceeds, not by methylation, but rather by demethylation of CH 3 SH to H 2 S and oxidation of H 2 S primarily to thiosulfate. MethodsTissues. Cecal and hepatic tissues were obtained from male Sprague-Dawley rats (300-400 g) while the animals were under pentobarbital anesthesia. The cecum was first cleansed of luminal debris by rinsing with isotonic saline, and the mucosa was then scraped off using the edge of a glass microscope slide. Tissue samples were maintained on ice until homogenized in an ice-cold buffer solution in a ratio of 1 part tissue to 15 parts buffer (wt/vol). Homogenization was performed with a Duall grinder (Kontes, Vineland, New Jersey, USA) with a Teflon pestle, using 8-10 strokes. Except when noted, studies were carried out using RPMI buffer, which has a pH of 7.4 when equilibrated with 5% CO 2 . This buffer contains a variety of electrolytes, including 0.4 mM sulfate. In addition, some studies were carried out in 0.1 M PBS (pH 7.0) or a buffer system containing 1.15% KCl, 5 mM Tris-HCl (pH 7.8), and 0.475 mM of the methyl donor S-adenosylmethionine, a milieu used in previously published studies (7) designed to assess thiol S-methyltransferase activity.Incubation studies. A 32-µL volume of homogenate or buffer was added to 20-mL polypropylene syringes. (Preliminary studies showed that bo...

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We assessed the effects of several treatments on the concentrations of oral sulfur-containing gases, compounds thought to be responsible for morning breath. Upon awakening in the morning, healthy volunteers collected oral gas samples before and for eight hours after the following treatments: no treatment, brushing the teeth with toothpaste, brushing the tongue, rinsing with 5 mL of 3% hydrogen peroxide, breakfast ingestion, or swallowing two BreathAsure capsules. The gas samples were analyzed for sulfur-containing volatiles via gas chromatography. Baseline collections usually contained three sulfur gases: hydrogen sulfide, methanethiol, and dimethylsulfide. The effectiveness of a treatment was determined via comparison of the areas under gas concentrations-time curves with and without treatment. Brushing the teeth or ingestion of BreathAsure had no apparent influence on the sulfur gases. Ingestion of breakfast and tongue brushing resulted in strong trends toward decreased sulfur gases. Hydrogen peroxide significantly reduced the sulfur gas concentrations for eight hours.

Soy flour derived from low-oligosaccharide soybeans resulted in less gas production than that derived from conventional soybeans.

The interaction of four cellular nucleophiles with the putative ultimate carcinogens N-sulfonoxy-2-[ring-3H]acetylaminofluorene (N-sulfonoxy-2-AAF) and N-acetoxy-2-[ring-3H] acetylaminofluorene (N-acetoxy-2-AAF), and with N-hydroxy-2-[ring-3H]acetylaminofluorene (N-hydroxy-2-AAF) activated to the ultimate carcinogens by enzymatic sulfonation or transacetylation was determined. The adducts were isolated and adduct formation was quantified by isotope dilution. The order of nucleophilicity of the acceptors was guanosine greater than tRNA congruent to polyguanylic acid (poly G) greater than N-acetyl-L-methionine when N-sulfonoxy-2-AAF, N-acetoxy-2-AAF or N-hydroxy-2-AAF activated by transacetylation were the electrophiles. In the case of N-hydroxy-2-AAF activated by enzymatic sulfonation, the order of nucleophilicity was N-acetyl-L-methionine greater than guanosine congruent to tRNA greater than poly G. The increase in the reactivity of N-acetyl-L-methionine is hypothesized to be due to cytosolic enzyme(s) which facilitate transfer of the methionine residue from the nitrogen to carbon atoms 3 and 1 of the fluorene moiety. Of the two synthetic esters, N-sulfonoxy-2- AAF exhibited greater electrophilicity than N-acetoxy-2-AAF. The rate of adduct formation of N-sulfonoxy-2-AAF and of N-acetoxy-2-AAF with each nucleophile was a function of nucleophile concentration, indicative of a bimolecular reaction mechanism. The interaction is thought to involve attack of the nucleophile on the uncharged ultimate carcinogen, although interaction with an ion pair cannot be eliminated. The mutagenicity of N-sulfonoxy-2-AAF, N-acetoxy-2-AAF and of enzymatically activated N-hydroxy-2-AAF was evaluated by the Ames test. N-Sulfonoxy-2-AAF was virtually inactive, while N-acetoxy-2-AAF exhibited weak mutagenicity. N-Hydroxy-2-AAF activated by enzymatic sulfonation exhibited greater mutagenicity than synthetic N-sulfonoxy-2-AAF. The mutagenicity and reactivity of ultimate carcinogens derived from N-hydroxy-2-AAF by enzymatic activation do not necessarily coincide with the mutagenicity and reactivity of the synthetic ultimate carcinogens.