Carcinogenicity in mice and rats of heterocyclic amines in cooked foods.

Ohgaki, Hideaki; Hasegawa, Hirokazu; Kato, Tomokazu; Suenaga, Miki; Ubukata, Mikiyo; Sato, Shigeaki; Takayama, Seiji; Sügimura, Takashi

doi:10.1289/ehp.8667129

Cited by 99 publications

(35 citation statements)

References 20 publications

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“…In fact, while many authors have found a positive association between HCA’s and breast, prostate, lung, and renal cancer (Ferrucci et al, 2009; Cross et al, 2005; Tasevska et al, 2009; Daniel et al, 2012), a recent prospective analysis revealed that intake of these meat-derived mutagens was not significantly associated with colorectal cancer risk (Le et al, 2016). Although studies have shown carcinogenic effects of both HCA and PAH mutagens in animal models, these experiments typically used doses higher than usual human exposure (Ohgaki et al, 1986; Magee, 1989). Regardless, compounds derived from metabolism of dietary aromatic amines have been suggested as biomarkers, to monitor carcinogenic effects in humans (Guo et al, 2016; Turesky and Le Marchand, 2011).…”

Section: Existing Theories To Explain Increased Disease Risks Of Rmentioning

confidence: 99%

Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid

Alisson-Silva

Kawanishi

Varki

2016

Molecular Aspects of Medicine

130

103

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One of the most consistent epidemiological associations between diet and human disease risk is the impact of red meat consumption (beef, pork, and lamb, particularly in processed forms). While risk estimates vary, associations are reported with all-cause mortality, colorectal and other carcinomas, atherosclerotic cardiovascular disease, type II diabetes, and possibly other inflammatory processes. There are many proposed explanations for these associations, some long discussed in the literature. Attempts to explain the effects of red meat consumption have invoked various red meat-associated agents, including saturated fat, high salt intake, Trimethylamine–N-oxide (TMAO) generation by microbiota, and environmental pollutants contaminating red meat, none of which are specific for red meat. Even the frequently mentioned polycyclic aromatic carcinogens arising from high temperature cooking methods are not red meat specific, as these are also generated by grilling poultry or fish, as well as by other forms of cooking. The traditional explanations that appear to be more red meat specific invoke the impact of N-nitroso compounds, heme iron, and the potential of heme to catalyze endogenous nitrosation. However, heme can be denatured by cooking, high levels of plasma hemopexin will block its tissue delivery, and much higher amounts of heme likely originate from red blood cell breakdown in vivo. Therefore, red meat-derived heme could only contribute to colorectal carcinoma risk, via direct local effects. Also, none of these mechanisms explain the apparent human propensity i.e., other carnivores have not been reported at high risk for all these diseases. A more recently proposed hypothesis involves infectious agents in beef from specific dairy cattle as agents of colorectal cancer. We have also described another mechanistic explanation for the human propensity for risk of red-meat associated diseases that is consistent with most observations: metabolic incorporation of a non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) into the tissues of red meat consumers and the subsequent interaction with inflammation-provoking antibodies against this “xenoautoantigen”. Overall, we conclude that while multiple mechanisms are likely operative, many proposed theories to date are not specific for red meat, and that the viral and xenoautoantigen theories deserve further consideration. Importantly, there are potential non-toxic dietary antidotes, if the xenoautoantigen is indeed correct.

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Section: Existing Theories To Explain Increased Disease Risks Of Rmentioning

confidence: 99%

Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid

Alisson-Silva

Kawanishi

Varki

2016

Molecular Aspects of Medicine

130

103

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“…The TD 50 values of the individual HAAs have been reported to range from 0.1 to 64.6 mg/kg/day in rodents (9) . The dose concentrations of HAAs used in these carcinogen bioassays were large: up to several hundred parts per million of HAA in the diet were given to rodents over a 2 year period (9,156) . However, the carcinogenic potency of some HAAs is markedly enhanced in experimental laboratory animals exposed to tumor promoters or agents that cause cell proliferation (9,157-159) .…”

Section: Introductionmentioning

confidence: 99%

Metabolism and Biomarkers of Heterocyclic Aromatic Amines in Molecular Epidemiology Studies: Lessons Learned from Aromatic Amines

Turesky

Marchand

2011

Chem. Res. Toxicol.

260

356

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Aromatic amines and heterocyclic aromatic amines (HAAs) are structurally related classes of carcinogens that are formed during the combustion of tobacco or during the high-temperature cooking of meats. Both classes of procarcinogens undergo metabolic activation by N-hydroxylation of the exocyclic amine group, to produce a common proposed intermediate, the arylnitrenium ion, which is the critical metabolite implicated in toxicity and DNA damage. However, the biochemistry and chemical properties of these compounds are distinct and different biomarkers of aromatic amines and HAAs have been developed for human biomonitoring studies. Hemoglobin adducts have been extensively used as biomarkers to monitor occupational and environmental exposures to a number of aromatic amines; however, HAAs do not form hemoglobin adducts at appreciable levels and other biomarkers have been sought. A number of epidemiologic studies that have investigated dietary consumption of well-done meat in relation to various tumor sites reported a positive association between cancer risk and well-done meat consumption, although some studies have shown no associations between well-done meat and cancer risk. A major limiting factor in most epidemiological studies is the uncertainty in quantitative estimates of chronic exposure to HAAs and, thus, the association of HAAs formed in cooked meat and cancer risk has been difficult to establish. There is a critical need to establish long-term biomarkers of HAAs that can be implemented in molecular epidemioIogy studies. In this review article, we highlight and contrast the biochemistry of several prototypical carcinogenic aromatic amines and HAAs to which humans are chronically exposed. The biochemical properties and the impact of polymorphisms of the major xenobiotic-metabolizing enzymes on the biological effects of these chemicals are examined. Lastly, the analytical approaches that have been successfully employed to biomonitor aromatic amines and HAAs, and emerging biomarkers of HAAs that may be implemented in molecular epidemiology studies are discussed.

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“…Heterocyclic amines (HAs) are an important group of food mutagens and potential carcinogens in rodents and primates [1,2]. At present, some 20 HAs have been isolated and identified at part per billion levels in proteinaceous foods after thermal processing, such as household cooking.…”

Section: Introductionmentioning

confidence: 99%