Dietary Nitrosamines from Processed Meat Intake as Drivers of the Fecal Excretion of Nitrosocompounds.

Diet is one of the main exogenous sources of potentially carcinogenic nitrosamines (NAs) along with tobacco and cosmetics. Several factors can affect endogenous N-nitroso compounds (NOCs) formation and therefore the potential damage of the intestinal mucosa at initial colorectal cancer stages. To address this issue, 49 volunteers were recruited and classified according to histopathological analyses. Lifestyle and dietary information were registered after colonoscopy. The mutagenicity of fecal supernatants was assayed by a modified Ames test. Fecal heme-derived NOCs and total NOC concentrations were determined by selective denitrosation and chemiluminescence-based detection. Results revealed processed meats as the main source of dietary nitrites and NAs, identifying some of them as predictors of the fecal concentration of heme-derived and total NOCs. Furthermore, increased fecal NOC concentrations were found as the severity of colonic mucosal damage increased from the control to the adenocarcinoma group, these concentrations being strongly correlated with the intake of the NAs N-nitrosodimethylamine, N-nitrosopiperidine, and N-nitrosopyrrolidine. Higher fecal NOC concentrations were also noted in higher fecal mutagenicity samples. These results could contribute to a better understanding of the importance of modulating dietary derived xenobiotics as related with their impact on the intestinal environment and colonic mucosa damage.

Genetic Variability Impacts Genotoxic and Transcriptome Responses in the Human Colon after the Consumption of Processed Red Meat Products and Those with Added Phytochemical Extracts.

The PHYTOME study investigated the effect of consuming processed meat products on outcomes related to colorectal cancer risk without testing the impact of genetic variability on these responses. This research aims to elucidate the genetic impact on apparent total N-nitroso compound (ATNC) excretion, colonic DNA adduct formation, ex vivo-induced DNA damage, and gene expression changes in colon biopsies of healthy participants. Through a systematic literature review, candidate polymorphisms were selected and then detected using TaqMan and PCR analysis. The effect of genotype on study outcomes was determined via a linear mixed model and analysis of variance. Machine learning was used to evaluate relative allele importance concerning genotoxic responses, which established a ranking of the most protective alleles and a combination of genotypes (gene scores). Participants were grouped by GSTM1 genotype and differentially expressed genes (DEGs), and overrepresented biological pathways were compared between groups. Stratifying participants by ten relevant genes revealed significant variations in outcome responses. After consumption of processed red meat, variations in NQO1 and COMT impacted responses in ATNC levels (µmol/L) (+9.56 for wildtype vs. heterozygous) and DNA adduct levels (pg/µg DNA) (+1.26 for variant vs. wildtype and +0.43 for variant vs. heterozygous), respectively. After phytochemicals were added to the meat, GSTM1 variation impacted changes in DNA adduct levels (-6.12 for deletion vs. wildtype). The gene scores correlated with these responses and DEGs were identified by GSTM1 genotype. The altered pathways specific to the GSTM1 wildtype group included 'metabolism', 'cell cycle', 'vitamin D receptor', and 'metabolism of water-soluble vitamins and co-factors'. Genotype impacted both the potential genotoxicity of processed red meat and the efficacy of protective phytochemical extracts.

Microbiota do megaesôfago e carcinogênese / Megaesophagus microbiota and carcinogenesis

INTRODUÇAO: O risco de desenvolvimento de carcinoma esofágico em portadores de megaesôfago é 33 vezes superior ao da populaçäo em geral. Possível explicaçäo para este fenômeno poderia estar relacionada à produçäo de compostos N-nitrosos na luz do órgäo, a partir da transformaçäo de nitratos da dieta em nitritos, mediada por bactérias em suspensäo no líquido de estase e com o contato crônico destes carcinógenos com a mucosa esofágica. OBJETIVO: Analisar a microbiota esofágica em pacientes portadores de megaesôfago de etiologia chagásica, com especial atençäo para a presença de bactérias com capacidade de reduçäo de nitratos. CASUíSTICA: Foram estudados prospectivamente 15 pacientes portadores de megaesôfago chagásico com idades variando de 28 a 73 anos, sendo 9 do sexo feminino e 6 do sexo masculino, que foram divididos em 3 grupos iguais de 5, de acordo com o grau de dilataçäo do esôfago, segundo a classificaçäo de Rezende et al. (Grau I, Grau II e Grau III). MÉTODO: A coleta do líquido de estase para estudo microbiológico era realizada através de sonda de Levine nº 14, que era passada pela boca, por dentro de uma cânula de intubaçäo orotraqueal nº 7,5, mantendo-se sua extremidade escondida, a fim de evitar sua contaminaçäo. RESULTADOS: Foram obtidas 93,3 por cento de culturas positivas com grande variedade de microrganismos e predomínio de aeróbios Gram-positivos e anaeróbios. As concentrações de microrganismos foram tanto maiores, quanto maior o grau de dilataçäo do esôfago. Entre os microrganismos encontrados, o Staphylococcus sp, Corynebacterium sp, Peptostreptococcus sp e a Veillonella sp foram aqueles identificados como tendo a capacidade de reduçäo de nitratos a nitritos. CONCLUSÄO: No megaesôfago chagásico há bactérias na luz do órgäo com capacidade de reduçäo de nitratos da dieta, passo importante na produçäo de compostos N-nitrosos.

Nitratos, nitritos e compostos N-nitrosos em alimentos: onde está o problema? / Nitrates, nitrites and N-nitrosocompounds in foods: where is the problem?

O objetivo deste artigo de revisäo é apresentar os problemas associados à presença de nitratos, nitritos e compostos. N-nitrosos em alimentos. Säo fornecidas informaçöes sobre as propriedades físico-químicas dos compostos, sua presença natural em vegetais e em alimentos processados, bem como os efeitos produzidos na exposiçäo humana: aspectos toxicológicos relacionados à ingestäo de nitratos e nitritos por adultos e crianças e á carcinogenicidade dos compostos N-nitrosos