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Interplay between heterocyclic amines in cooked meat and metabolic phenotype in the etiology of colon cancer.

Although the etiology of colon cancer remains uncertain, an increasing body of epidemiologic evidence indicates that red meat consumption is an important risk factor. The cooking of red meat produces a class of potent experimental carcinogens, the heterocyclic aromatic amines (HAA). These induce cancers in several different sites, including the colon, in rats and mice. Other epidemiologic studies indicate that an individual's genetically determined metabolic phenotype (polymorphisms for N-acetyltransferase and N-hydroxylase) modulates the risk of colon cancer. Both N-acetyltransferase and N-hydroxylase are involved in the metabolism of HAA. An increased risk of colon cancer has been observed in rapid acetylators in four of five studies; further, in two of these the association was found only in meat eaters. The latter observation supports the hypothesis that HAA are involved in colon carcinogenesis. Considerable progress has been made in the study of the molecular pathogenesis of colon cancer, which typically entails the cumulation of several genetic events (mutations and deletions) in oncogenes and tumor suppressor genes. It would now be a crucial contribution to elucidating the causation of colon cancer to show that such mutations are induced in human colonic mucosa by food-borne heterocyclic aromatic amines.

Amines↗

Case-control study on the role of heterocyclic amines in the etiology of upper aerodigestive cancers in Uruguay.

To examine the risk of upper aerodigestive tract cancers (UADC: oral cavity, pharynx, larynx, and esophagus) associated with dietary heterocyclic amine (HCA) exposure, a case-control study involving 140 cases and 286 controls was conducted in Montevideo, Uruguay. Beef and red meat intakes were positively associated with risk of UADC [odds ratio (OR) for red meat intake = 2.8, 95% confidence interval (CI) = 1.4-6.0], whereas no association was observed with white meat (poultry plus fish) intake. When meat intake was examined by cooking method, no association was observed for fried meat. On the other hand, broiled and boiled meat were associated with a significant increase in risk of UADC (OR for broiled meat = 2.0, 95% CI = 1.0-4.3). Total HCA intake was associated with an increased risk (OR = 2.2, 95% CI = 1.1-4.2) of UADC. The HCA effect was similar among the different cancer sites.

Adult↗

GSTM-1 and NAT2 and genetic alterations in colon tumors.

OBJECTIVE: Phase II metabolizing enzymes such as glutathione S-transferases and N-acetyltransferase are involved in the detoxification of carcinogens. Genetic variants of genes coding for these enzymes have been evaluated as to their association with colon cancer, both as independent risk factors and as effect modifiers for associations with diet and cigarette smoking. In this study, we evaluate associations between the GSTM-1 genotype and the NAT2-imputed phenotype and acquired mutations in tumors. METHODS: Data is taken from a set of 1836 cases and 1958 controls with colon cancer who were part of a large case-control study of colon cancer and whose tumors were previously analyzed for Ki-ras, p53, and microsatellite instability (MSI). We also evaluate the modifying effects of these genetic variants with diet and cigarette smoking, factors previously identified as being associated with specific tumor alterations. RESULTS: Neither GSTM-1 nor the NAT2-imputed phenotype was independently associated with Ki-ras, p53, or MSI. Cigarette smoking significantly increased the risk of tumors involving the MSI pathway. Additionally, cigarette smoking doubled the risk of p53 transversion mutations among those who were GSTM-1 present. Cases were slightly more likely to have a p53 mutation if they frequently consumed red meat and had the imputed NAT2 intermediate/rapid phenotype relative to slow phenotype/infrequent consumers of red meat (OR 2.0, 95% CI 1.3-3.0 for intermediate/rapid). CONCLUSIONS: These data provide support that diet and cigarette smoking may be associated with specific disease pathways, although GSTM-1 and NAT2 do not independently appear to alter susceptibility to these diet and lifestyle factors.

Adult↗

Slaughter of deer.

Deer farming in the British Isles is in its infancy but the industry is growing. Deer farmers retail their own venison from the farm having shot individual deer at close range as they graze. Although the method of killing is effective, humane and does not alarm the other deer, it is primitive. It is essential that as the industry expands, the normal retail channels used by the producers of other livestock be opened to deer farmers by means of appropriate legislation. Research into the special needs in slaughterhouses for deer is being undertaken, particularly in the lairage and devising a safe humane means of delivery to the point of slaughter. At the slaughter unit on Glensaugh experimental deer farm, a captive bolt pistol is used in a specially designed stunning pen. The carcases are prepared for sale in skin to the game trade, but environmental conditions are unsuitable for preparation of red meat for sale. However in-skin carcases have been transferred later to the red meat trade and prepared as boned out convenience packs.

Abattoirs↗

Prospective study of plasma fatty acids and risk of prostate cancer.

BACKGROUND: Although some evidence suggests that dietary fat intake is related to prostate cancer, epidemiologic studies have been inconsistent. PURPOSE: Our purpose was to assess the association between plasma lipid levels, particularly linoleic and alpha-linolenic acids, and the development of prostate cancer. METHODS: In 1982, at the start of the Physicians' Health Study, 14916 U.S. male physicians provided plasma samples, which were frozen at -82 degrees C. Data accumulated from a series of questionnaires were used to assess the intake of various foods. We used a nested case-control design to compare the fatty acid compositions in plasma from 120 men who later developed prostate cancer with 120 matched controls who did not. Individual fatty acids were measured in plasma as a percentage of total fatty acids, using capillary gas chromatography. Conditional logistic regression models were used to obtain odds ratio estimates while adjusting simultaneously for the effects of one or more potential confounders. RESULTS: The relative risks (RRs) of prostate cancer for men in successively higher quartiles of plasma alpha-linolenic acid level were 3.0 (95% confidence interval [CI] = 1.2-7.3), 3.4 (95% CI = 1.6-7.5), and 2.1 (95% CI = 0.9-4.9), compared with those with levels below the detection threshold (P trend = .03). For linoleic acid, RRs in successively higher quartiles were 0.7 (95% CI = 0.4-1.5), 0.8 (95% CI = 0.4-1.6), and 0.6 (95% CI = 0.3-1.3), with the lowest quartile as referent (P trend = .24). The effect estimates were not notably altered by adjustment for exercise, body mass, meat and dairy consumption, or other fatty acid levels in the plasma. The RR for eating red meat at least five times per week compared with less than once a week was 2.5 (95% CI = 0.9-6.7) and was little changed by adjustment for alpha-linolenic acid, although alpha-linolenic acid levels were correlated with intake of red meat and butter. The association of alpha-linolenic acid levels with prostate cancer was greater among men with low linoleic acid and reduced meat intake. CONCLUSIONS: These results suggest that low plasma levels of alpha-linolenic acid might be associated with reduced risk of prostate cancer, independently of high meat intake. High linoleic acid and low marine fatty oils were not associated with increased risk, as previously hypothesized. IMPLICATIONS: The effects of dietary alpha-linolenic acid, particularly from vegetable sources, warrant further study. The effects of dietary linoleic acid and marine fatty acids seen in animal bioassays might not apply to human prostate cancer.

Aged↗

[Colorectal cancer: controversial role of meat consumption].

Diet is supposed to influence the colorectal cancer etiology, but the precise causative factors are yet unknown. International ecological studies show a strong correlation between meat consumption and the colorectal cancer incidence. Most case-control studies (22 of 29) show an increased risk to develop a colorectal cancer for those eating higher amounts of meat. In contrast, only 2 out of the 5 best prospective cohort studies have shown this positive association for red meat. Two studies out of 4 show an association with processed meat. Consumption of white meat or of fish is not associated with a high risk, and might even reduce the occurrence of colorectal cancer. Several plausible hypotheses concerning the link between meat and colon carcinogenesis have been suggested. They involve saturated fat, protein, iron, heterocyclic amines produced by cooking, and N-nitroso compounds. High fat diets may promote cancer because they have a high caloric content, or because they lead to increased levels of bile acids in the colonic lumen. Six experimental studies are published on the effect of meat, or meat fractions, on the colon tumor incidence in rodents initiated with chemical carcinogens. Data from these studies do not support the belief that red meat (beef) has a specific effect on intestinal carcinogenesis. Instead, diets containing beef meat (cooked or raw) decrease carcinogenesis when compared to control diets containing similar amounts of fat and protein of vegetal origin. However, high fat or high protein diets often increase carcinogenesis when compared to low fat or low protein diets. Thus, one cannot state, nor exclude, that meat promotes colorectal cancer.

Amines↗

A prospective study of dietary patterns, meat intake and the risk of gestational diabetes mellitus.

AIMS/HYPOTHESIS: The aim of this study was to prospectively examine whether dietary patterns are related to risk of gestational diabetes mellitus (GDM). METHODS: This prospective cohort study included 13,110 women who were free of cardiovascular disease, cancer, type 2 diabetes and history of GDM. Subjects completed a validated semi-quantitative food frequency questionnaire in 1991, and reported at least one singleton pregnancy between 1992 and 1998 in the Nurses' Health Study II. Two major dietary patterns (i.e. 'prudent' and 'Western') were identified through factor analysis. The prudent pattern was characterised by a high intake of fruit, green leafy vegetables, poultry and fish, whereas the Western pattern was characterised by high intake of red meat, processed meat, refined grain products, sweets, French fries and pizza. RESULTS: We documented 758 incident cases of GDM. After adjustment for age, parity, pre-pregnancy BMI and other covariates, the relative risk (RR) of GDM, comparing the highest with the lowest quintile of the Western pattern scores, was 1.63 (95% CI 1.20-2.21; p (trend)=0.001), whereas the RR comparing the lowest with the highest quintile of the prudent pattern scores was 1.39 (95% CI 1.08-1.80; p (trend)=0.018). The RR for each increment of one serving/day was 1.61 (95% CI 1.25-2.07) for red meat and 1.64 (95% CI 1.13-2.38) for processed meat. CONCLUSIONS/INTERPRETATION: These findings suggest that pre-pregnancy dietary patterns may affect women's risk of developing GDM. A diet high in red and processed meat was associated with a significantly elevated risk.

Adult↗

Meat, poultry, and fish consumption and nutrient intake in the healthy elderly.

Food selection of the healthy elderly may be influenced by life-styles, the food supply, and recommendations related to diet and disease. This study used food group analysis of 3-day diet records to examine red meat, poultry, and fish consumption by free-living, healthy elderly individuals. Dietary data were from 122 women and 97 men (median age = 75 years) who were participants in the New Mexico Aging Process Study in 1984. Mean dietary intake was 1,494 kcal/day for women and 2,079 kcal/day for men--82% and 94% of the Recommended Dietary Allowance (RDA), respectively. Protein, iron, and selected B vitamins were above 100% of the RDA. Women's mean daily intake of meat/poultry/fish was 87.7 g (52.1 g meat, 23.6 g poultry, 12.0 g fish); men's intake of meat/poultry/fish was 121.2 g (78.4 g meat, 21.2 g poultry, 21.6 g fish). Of the total red meat, more than 50% was beef, 20% was pork/ham, and more than 10% was processed meat. For women, meat/poultry/fish provided 14% of total dietary energy, 37% of protein, 13% to 32% of selected B vitamins and iron, 20% of fat, and 34% of cholesterol. Percentages were similar for men. There was no significant association between age and total dietary intake, but food group consumption had distinct associations with age for women and men. Our findings indicate that a moderate but not excessive intake of meat/poultry/fish made a substantial contribution to nutrient intake. The fat contribution of these food groups could be decreased by emphasizing lower-fat selections of meat, poultry, and fish.

Age Factors↗

Breast cancer, heterocyclic aromatic amines from meat and N-acetyltransferase 2 genotype.

Breast cancer risk has been hypothesized to increase with exposure to heterocyclic aromatic amines (HAAs) formed from cooking meat at high temperature. HAAs require enzymatic activation to bind to DNA and initiate carcinogenesis. N-acetyltransferase 2 (NAT2) enzyme activity may play a role, its rate determined by a polymorphic gene. We examined the effect of NAT2 genetic polymorphisms on breast cancer risk from exposure to meat by cooking method, doneness and estimated HAA [2-amino-1-methyl-6-phenylimidazole[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)] intake. Women were recruited with suspicious breast masses and questionnaire data were collected prior to biopsy to blind subjects and interviewers to diagnoses. For 114 cases with breast cancer and 280 controls with benign breast disease, NAT2 genotype was determined using allele-specific PCR amplification to detect slow acetylator mutations. HAAs were estimated from interview data on meat type, cooking method and doneness, combined with a quantitative HAA database. Logistic regression models controlled for known risk factors, first including all controls, then 108 with no or low risk (normal breast or no hyperplasia) and finally 149 with high risk (hyperplasia, atypical hyperplasia, complex fibroadenomas). Meat effects were examined within NAT2 strata to assess interactions. We found no association between NAT2 and breast cancer. These Californian women ate more white than red meat (control median 46 versus 8 g/day). There were no significant associations of breast cancer with red meat for any doneness. White meat was significantly protective (>67 versus <26 g/day, OR 0.46, 95% CI 0.23-0.94, P for trend = 0.02), as was chicken, including well done, pan fried and barbecued chicken. MeIQx and DiMeIQx were not associated with breast cancer. A protective effect of PhIP was confounded after controlling for well done chicken. Results were unchanged using low or high risk controls or dropping 30 in situ cases. There was no interaction between NAT2 and HAAs. These findings do not support a role for HAAs from meat or NAT2 in the etiology of breast cancer. Further research is needed to explain the white meat association.

Adult↗

K-ras mutations, rectal crypt cells proliferation, and meat consumption in patients with left-sided colorectal carcinoma.

It has been suggested that N-nitroso compounds derived from meat may increase the risk of K-ras mutations in the human colon. We sought evidence of associations between red meat consumption, frequency and type of K-ras mutations in resected tumours, and the rate of crypt cell proliferation (CCP) in the normal mucosa of patients with left-sided colorectal carcinoma. Meat consumption was assessed by food frequency questionnaire, and CCP was determined in rectal biopsies obtained prior to surgery. K-ras mutations in the resected tumours were determined using a PCR-based oligonucleotide hybridization assay. Fifteen K-ras mutations were detected in tumours from 43 patients; 13/15 in codon 12, 3/15 in codon 13, and 1/15 in both codons 12 and 13. All mutations were G-->A or G-->T transitions. There was no statistically significant difference between intakes of red meat in patients with a K-ras mutation (92.4 +/- 9.7 g/day) and those without (82.3 +/- 7.7 g/day). Rectal CCP was significantly higher in patients than in healthy controls, but there was no correlation with meat consumption or K-ras mutation. These data do not support the hypothesis that meat consumption is a risk factor for acquisition of K-ras mutations during colorectal carcinogenesis.

Aged↗

Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas.

High red meat intake has been linked with an increased risk of colorectal cancer and adenomas. During high temperature cooking of red meats, heterocyclic amines (HCAs) are generated; however, to be carcinogenic, they must be metabolized by enzymes including cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 (NAT1) and/or N-acetyltransferase 2 (NAT2). We have conducted a clinic-based case-control study of colorectal adenomas that focused on assessment of exposure to HCAs (estimated by use of a HCA database and meat cooking module) and modification of these exposures by genetic factors. We have previously reported that intake of MeIQx was associated with an increased risk of colorectal adenomas [overall association at 80th percentile, > 27.00 ng/day: odds ratio (OR) = 2.68, 95% confidence interval (CI) 1.58-4.55]. Here, we report our evaluation of whether variation in CYP1A2, NAT1 and/or NAT2 modify the association between HCAs and colorectal adenoma formation in 146 cases and 228 frequency-matched controls. The NAT1*10 allele was associated with a nonsignificant increased risk of colorectal adenomas (OR = 1.43; 95% CI 0.86-2.36). Further, when we analysed 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake as a categorical variable, we observed a six-fold increase in adenoma risk among rapid NAT1 acetylators who consumed more than 27 ng a day (OR = 6.50; 95% CI 2.16-19.7), whereas among slow NAT1 acetylators, the increase in risk was two-fold (OR = 2.32; 95% CI 1.12-4.81). While suggestive, the results were not significantly different from each other on either an additive or multiplicative scale. In contrast, NAT2 genotype and CYP1A2 and NAT2 hepatic activity measured by caffeine urinary metabolites were not associated with adenoma risk, although an increase in risk with rapid CYP1A2 activity could not be ruled out (OR = 1.46; 95% CI 0.76-2.81). Moreover, there was no evidence that the effect of MeIQx was enhanced among subjects in any subgroup defined by variation in these measures. These results are compatible with the hypothesis that high HCA exposure is associated with an increased risk of colorectal adenomas, particularly in genetically susceptible subgroups. Further study of larger populations is needed to confirm and extend these observations.

Adenoma↗

Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women.

BACKGROUND: The rates of colon cancer in various countries are strongly correlated with the per capita consumption of red meat and animal fat and, to a lesser degree, inversely associated with the consumption of fiber. METHODS: We conducted a prospective study among 88,751 women 34 to 59 years old and without a history of cancer, inflammatory bowel disease, or familial polyposis who completed a dietary questionnaire in 1980. By 1986, during 512,488 person-years of follow-up, 150 incident cases of colon cancer had been documented. RESULTS: After adjustment for total energy intake, animal fat was positively associated with the risk of colon cancer (P for trend = 0.01); the relative risk for the highest as compared with the lowest quintile was 1.89 (95 percent confidence interval, 1.13 to 3.15). No association was found for vegetable fat. The relative risk of colon cancer in women who ate beef, pork, or lamb as a main dish every day was 2.49 (95 percent confidence interval, 1.24 to 5.03), as compared with those reporting consumption less than once a month. Processed meats and liver were also significantly associated with increased risk, whereas fish and chicken without skin were related to decreased risk. The ratio of the intake of red meat to the intake of chicken and fish was particularly strongly associated with an increased incidence of colon cancer (P for trend = 0.0005); the relative risk for women in the highest quintile of this ratio as compared with those in the lowest quintile was 2.49 (95 percent confidence interval, 1.50 to 4.13). A low intake of fiber from fruits appeared to contribute to the risk of colon cancer, but this relation was not statistically independent of meat intake. CONCLUSIONS: These prospective data provide evidence for the hypothesis that a high intake of animal fat increases the risk of colon cancer, and they support existing recommendations to substitute fish and chicken for meats high in fat.

Adult↗

Natural chlorophyll but not chlorophyllin prevents heme-induced cytotoxic and hyperproliferative effects in rat colon.

Diets high in red meat and low in green vegetables are associated with an increased risk of colon cancer. In rats, dietary heme, mimicking red meat, increases colonic cytotoxicity and proliferation of the colonocytes, whereas addition of chlorophyll from green vegetables inhibits these heme-induced effects. Chlorophyllin is a water-soluble hydrolysis product of chlorophyll that inhibits the toxicity of many planar aromatic compounds. The present study investigated whether chlorophyllins could inhibit the heme-induced luminal cytotoxicity and colonic hyperproliferation as natural chlorophyll does. Rats were fed a purified control diet, the control diet supplemented with heme, or a heme diet with 1.2 mmol/kg diet of chlorophyllin, copper chlorophyllin, or natural chlorophyll for 14 d (n = 8/group). The cytotoxicity of fecal water was determined with an erythrocyte bioassay and colonic epithelial cell proliferation was quantified in vivo by [methyl-(3)H]thymidine incorporation into newly synthesized DNA. Exfoliation of colonocytes was measured as the amount of rat DNA in feces using quantitative PCR analysis. Heme caused a >50-fold increase in the cytotoxicity of the fecal water, a nearly 100% increase in proliferation, and almost total inhibition of exfoliation of the colonocytes. Furthermore, the addition of heme increased TBARS in fecal water. Chlorophyll, but not the chlorophyllins, completely prevented these heme-induced effects. In conclusion, inhibition of the heme-induced colonic cytotoxicity and epithelial cell turnover is specific for natural chlorophyll and cannot be mimicked by water-soluble chlorophyllins.

Animals↗

Beef tallow increases apoptosis and decreases aberrant crypt foci formation relative to soybean oil in rat colon.

Although epidemiological studies have implicated red meat as increasing colon cancer risk, animal studies have generally not been supportive of such an effect. This study examined red meat components, such as beef protein and tallow, on markers of colon cancer risk. Rats administered dimethylhydrazine were fed either casein or beef protein as the protein source and soybean oil or tallow as the fat source in a 2 2 factorial design for 9 wk. There were fewer preneoplastic lesions [aberrant crypt foci (ACF)] and a greater apoptotic labeling index (P < 0.05) in the distal colonic mucosa of rats fed tallow compared with soybean oil. Fecal bile acid concentrations were significantly lower in rats fed tallow compared with soybean oil. There were no significant differences in mucosal cell proliferation. No significant effects were found due to protein source or to interactions between fat and protein sources for ACF, cell proliferation labeling indexes, or bile acid concentrations. However, there was a significant protein by fat source interaction for the apoptotic labeling index. The decreased number of ACF, decreased fecal bile acid concentration, and increased mucosal apoptosis with tallow consumption are not consistent with a role for this fat in increasing risk of colon cancer.

1,2-Dimethylhydrazine↗

A technique for field measurement of knife sharpness.

Knife sharpness can affect the productivity of meatpacking operations as well as the forces to which meat cutters are exposed. This report describes the development and evaluation of a "sharpness tester" designed to meet the criteria that the system be portable for field use at meatpacking plants, requires no special skills to operate, provides a non-destructive test of the entire blade edge, and incorporates a test motion that is representative of meat cutting. The system was bench tested for sensitivity to incremental changes in blade sharpness; suitability of the test material as a surrogate for red meat; and ability to detect variations in sharpness along the length of the blade. A graphical presentation showed that changes in cutting forces measured with the system correspond to changes in blade sharpness. Measurements made with both the test material and with red meat showed good correlation (r = 0.89). The system demonstrated the capacity to detect differences in sharpness in regions of a knife edge as well as providing visual evidence of defects along the edge of a knife blade.

Equipment Design↗

Nutrition and cancer.

Evidence from both animal and epidemiologic studies indicate that throughout life excessive energy intake in relation to requirements increases risk of human cancer. Rapid growth rates in childhood lead to earlier age at menarche, which in turn increases risk of breast cancer, and accumulation of body fat in adulthood in related to cancers of the colon, kidney, and endometrium as well as postmenopausal breast cancer. Higher intake of vegetables and fruits has been associated with lower risks of many cancers. The constituents responsible for these apparent protective effects remain uncertain, although evidence supports a contribution of folic acid. Recent evidence suggests that the percentage of energy from fat in the diet is not a major cause of cancers of the breast or colon. Higher intake of meat and dairy products has been associated with greater risk of prostate cancer, which may be related to their saturated fat content. Also, red meat consumption has been associated with risk of colon cancer in numerous studies, but this appears to be unrelated to its fat content. Excessive consumption of alcohol increases risks of upper gastrointestinal tract and even moderate intake appears to increase cancers of the breast and large bowel. Although many details remain to be learned, evidence is strong that remaining physically active and lean throughout life, consuming an abundance of fruits and vegetables, and avoiding high intakes of red meat, foods high in animal fat, and excessive alcohol will substantially reduce risk of human cancer.

Breast Neoplasms↗

Quantitative biomechanical analysis of wrist motion in bone-trimming jobs in the meat packing industry.

This study was motivated by the serious impact that cumulative trauma disorders (CTDs) of the upper extremities have on the meat packing industry. To date, no quantitative data have been gathered on the kinematics of hand and wrist motion required in bone-trimming jobs in the red-meat packing industry and how these motions are related to the risk of CTDs. The wrist motion of bone-trimming workers from a medium-sized plant was measured, and the kinematic data were compared to manufacturing industry's preliminary wrist motion benchmarks from industrial workers who performed hand-intensive, repetitive work in jobs that were of low and high risk of hand/wrist CTDs. Results of this comparison show that numerous wrist motion variables in both the left and right hands of bone-trimming workers are in the high-risk category. This quantitative analysis provides biomechanical support for the high incidence of CTDs in the meat packing industry. The research reported in this paper established a preliminary database of wrist and hand kinematics required in bone-trimming jobs in the red-meat packing industry. This kinematic database could augment the industry's efforts to reduce the severity and cost of CTDs. Ergonomics practitioners in the industry could use the kinematic methods employed in this research to assess the CTD risk of jobs that require repetitious, hand-intensive work.

Biomechanical Phenomena↗

Mucosal pentraxin (Mptx), a novel rat gene 10-fold down-regulated in colon by dietary heme.

Consumption of red meat is associated with increased colon cancer risk. Our previous work indicated that this association might be due to the heme content of red meat. In rat studies, dietary heme increased colonic cytotoxicity and epithelial cell turnover, carcinogenesis biomarkers. Here we apply DNA microarray technology to examine effects of heme on colonic gene expression. A rat colon-specific microarray was constructed and hybridized in duplicate to RNA extracts from colon scrapings of rats fed diets with or without heme (n=6-7). We were able to reproducibly identify changes in colonic mRNA abundance in response to heme. Most striking was a >10-fold down-regulation of a single rat gene, an unprecedented gene-modulating effect of a dietary component. Based on homology, the novel gene encodes a pentraxin, the first identified in colon. Pentraxins are postulated to be involved in dealing with dying cells. Quantitative PCR confirmed the strong heme-induced down-regulation of this gene, which we named mucosal pentraxin (Mptx). Overall, our data support the efficacy of cDNA array expression profiling to investigate effects of specific nutrients in an in vivo system and may provide an approach to establishing markers for diet-induced stress of mammalian colonic mucosa.

Acute-Phase Proteins↗