Suggestive evidence for the induction of colonic aberrant crypts in mice fed sodium nitrite.

A reported linkage between processed (nitrite-treated) meat products and the incidence of colon cancer could be due to sodium nitrite (NaNO2) itself or to N-nitroso compounds produced from the nitrite. Exposure to nitrite occurs due to residual nitrite in processed meat and to salivary nitrite arising by reduction of nitrate in vegetables and drinking water. Here we tested whether NaNO2 could induce colonic aberrant crypts (ABC) or ABC foci (ACF), which are putative precursors of colon cancer.

Urinary excretion of N-nitroso compounds in rats fed sodium nitrite and/or hot dogs.

Nitrite-treated meat is a reported risk factor for colon cancer. Mice that ingested sodium nitrite (NaNO2) or hot dogs (a nitrite-treated product) showed increased fecal excretion of apparent N-nitroso compounds (ANC). Here, we investigated for the first time whether rats excrete increased amounts of ANC in their urine after they are fed NaNO2 and/or hot dogs.

Developmental abnormalities in chicken embryos exposed to N-nitrosoatrazine.

Nitrate and atrazine (ATR) occur in combination in some drinking-water supplies and might react to form N-nitrosoatrazine (NNAT), which is reportedly more toxic than nitrate, nitrite, or ATR. Current evidence from population-based studies indicates that exposure to nitrate, nitrite, and nitrosatable compounds increases the risk of congenital defects and/or rate of embryo lethality. To test the hypothesis that NNAT induces malformations during embryogenesis, chicken embryos were examined for lethality and developmental abnormalities after treating fertilized eggs with 0.

Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers.

Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats.

Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat-induced preneoplastic lesions in rats and associated biomarkers in rats and humans.

Calcium inhibits promotion by hot dog of 1,2-dimethylhydrazine-induced mucin-depleted foci in rat colon.

Epidemiology suggests that processed meat is associated with colorectal cancer risk, but few experimental studies support this association. We have shown that a model of cured meat made in a pilot workshop promotes preneoplastic lesions, mucin-depleted foci (MDF) in the colon of rats. This study had two aims: to check if real store-bought processed meats also promote MDF, and to test if calcium carbonate, which suppresses heme-induced promotion, can suppress promotion by processed meat.

Supercritical fluid technology based large porous celecoxib-PLGA microparticles do not induce pulmonary fibrosis and sustain drug delivery and efficacy for several weeks following a single dose.

Although pulmonary dosing of large porous particles has been shown to sustain drug delivery for a few days, there are no reports on safety or long term delivery. In this study we prepared large porous poly(lactide-co-glycolide) (PLGA) microparticles of celecoxib using supercritical fluid pressure-quench technology and demonstrated 4.8-, 15.

Induction of colonic aberrant crypts in mice by feeding apparent N-nitroso compounds derived from hot dogs.

Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds.

Effect of feeding nitrite, ascorbate, hemin, and omeprazole on excretion of fecal total apparent N-nitroso compounds in mice.

It was proposed that colon cancer induced by red and nitrite-preserved meat is due to meat-derived N-nitroso compounds in the colonic contents. To explore this view, we previously showed that feeding beef and hot dogs increased the fecal output of total apparent N-nitroso compounds (ANC) in mice. In the current project, adult Swiss mice were fed a semipurified diet and water containing additives for 7 days.

Public health implications of smokeless tobacco use as a harm reduction strategy.

Harm reduction strategies involve promoting a product that has adverse health consequences as a substitute for one that has more severe adverse health consequences. Smokeless tobacco low in nitrosamine content offers potential benefits in reducing smoking prevalence rates. Possible harm arises from the potential for such products to serve as a gateway to more harmful tobacco products, public misinterpretation of "less harmful" as "safe," distraction from the public health goal of tobacco elimination, and ethical issues involved in advising those marketing these harmful products.

Partial purification from hot dogs of N-nitroso compound precursors and their mutagenicity after nitrosation.

Hot dogs contain apparent N-nitroso compounds (ANC) and ANC precursors (ANCP). ANCP purification was followed by nitrosation, sulfamic acid treatment, and analysis for ANC. Aqueous hot dog extracts were adsorbed on silica gel, which was eluted with MeCN and MeOH.

Comparative analysis of tobacco-specific nitrosamines and total N-nitroso compounds in moldovan cigarette tobacco.

While previous studies have evaluated levels of tobacco-specific nitrosamines (TSNA) and total N-nitroso compounds (NOC) in tobacco, there are no reports in the literature on TSNA and total NOC in the same tobacco products. We compared levels of TSNA, total NOC, and NOC precursors (NOCP) in tobacco of cigarettes purchased in Moldova and in some tobacco types commonly used for the manufacturing of Moldovan cigarettes. Cigarette tobaccos included those from non-Moldovan, traditional Moldovan, and blended Moldovan cigarettes.

Inhibition by allyl sulfides and crushed garlic of O6-methylguanine formation in liver DNA of dimethylnitrosamine-treated rats.

Garlic consumption is linked with lower incidences of certain cancers perhaps because garlic-derived allyl sulfides inhibit nitrosamine activation by cytochrome P450s. To help evaluate this view, effects of allyl sulfides on O6-methylguanine (O6MG) levels were examined in liver of rats injected with 20 mg/kg of liver carcinogen dimethylnitrosamine (DMN) and killed 3 h later. DNA was isolated and hydrolyzed, and O6MG/guanine ratios were determined by HPLC-fluorescence.

Inhibition by allyl sulfides and phenethyl isothiocyanate of methyl-n-pentylnitrosamine depentylation by rat esophageal microsomes, human and rat CYP2E1, and Rat CYP2A3.

Garlic and Cruciferae are associated with reduced risks of several human cancers, and some of their constituents are anticarcinogenic in animals. Here we studied inhibition of in vitro metabolism of the rat esophageal carcinogen methyl-n-pentylnitrosamine (MPN) by garlic-derived allyl sulfides and by Cruciferae-derived phenethyl isothiocyanate (PEITC) and sulforaphane. The test inhibitors were incubated with [3H]-MPN, NADPH-generating system and rat esophageal microsomes (REM) or a cytochrome P450 (CYP).

Nitrosation of glycine ethyl ester and ethyl diazoacetate to give the alkylating agent and mutagen ethyl chloro(hydroximino)acetate.

Whereas nitrosation of secondary amines produces nitrosamines, amino acids with primary amino groups and glycine ethyl ester were reported to react with nitrite to give unidentified agents that alkylated 4-(p-nitrobenzyl)pyridine to produce purple dyes and be direct mutagens in the Ames test. We report here that treatment of glycine ethyl ester at 37 degrees C with excess nitrite acidified with HCl, followed by ether extraction, gave 30-40% yields of a product identified as ethyl chloro(hydroximino)acetate [ClC(=NOH)COOEt, ECHA] and a 9% yield of ethyl chloroacetate. The ECHA was identical to that synthesized by a known method from ethyl acetoacetate, strongly alkylated nitrobenzylpyridine, and may have arisen by N-nitrosation of glycine ethyl ester to give ethyl diazoacetate, which was C-nitrosated and reacted with chloride to give ECHA.

N-nitroso compounds in the gastrointestinal tract of rats and in the feces of mice with induced colitis or fed hot dogs or beef.

Because colonic N-nitroso compounds (NOC) may be a cause of colon cancer, we determined total NOC levels by Walters' method in the gastrointestinal tract and feces of rodents: (i) feces of C57BL mice fed chow and semi-purified diets contained 3.2 +/- 0.4 and 0.

Total N-nitroso compounds and their precursors in hot dogs and in the gastrointestinal tract and feces of rats and mice: possible etiologic agents for colon cancer.

We review evidence that red and processed meat are causes of colon cancer and that processed meat is a risk factor for childhood cancer and type 2 diabetes. Associations could be due to N-nitroso compounds (NOCs) derived from nitrosation of NOC precursors (NOCPs). We review our survey of total NOC and NOCP content of foods.