Experimental study of the therapeutic effects of folate, vitamin A, and vitamin B12 on squamous metaplasia of the bronchial epithelium

Kamei, Tamiko; Kohno, Toshihiko; Ohwada, Hayato; Takeuchi, Yuka; Hayashi, Yutaka; Fukuma, S

doi:10.1002/1097-0142(19930415)71:8<2477::aid-cncr2820710809>3.0.co;2-g

Cited by 28 publications

(8 citation statements)

References 25 publications

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“…26 Kamei et al reported that epithelial hyperplasia and metaplasia of the respiratory tract induced by methylcholanthrene was suppressed by administration of folic acid. 27 In our study, only 3/8 beagles developed gastric cancer in the folic acid treated group. However, all eight dogs in the control group who did not receive folic acid developed gastric cancer.…”

Section: Discussionmentioning

confidence: 48%

Interventional study of high dose folic acid in gastric carcinogenesis in beagles

Xiao

Meng²,

Shi³

et al. 2002

Gut

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Background: A decrease in folic acid and subsequent DNA hypomethylation may be involved in gastric carcinogenesis. Epidemiological and nutritional studies have indicated that folate status modulates the risk of developing cancers. Aims: To investigate whether folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by N-ethyl-N-nitrosoguanidine (ENNG) in beagles. Methods: Sixteen male beagles were randomly divided into two groups: folic acid treated group and control group. In both groups beagles were fed ENNG 75 mg per day for eight months and in the treated group 20 mg folic acid was given to beagles for 15 months. Gastroscopy and biopsies were performed before and every 2-3 months after administration of ENNG until the end of the experiment. Histopathological lesions were diagnosed with regard to the criteria for human gastric mucosal biopsies. Serum and gastric mucosal tissue folic acid concentrations were measured. Results: In the control group, all beagles developed gastric cancer (8/8) compared with only 3/8 in the folic acid treated group (p<0.05). Moreover, serum and gastric mucosal tissue folic acid concentrations were markedly elevated 15 months after folic acid administration. The difference was statistically significant between the two groups (p<0.05). Conclusions: Our results indicate that high dose folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by a chemical carcinogen ENNG in beagles.

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Section: Discussionmentioning

confidence: 48%

Interventional study of high dose folic acid in gastric carcinogenesis in beagles

Xiao

Meng²,

Shi³

et al. 2002

Gut

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“…Folate deficiencies have also been shown to play a role in Downs syndrome (Hobbs et al 2000), neural tube defects (MRC vitamin study research group 1991), pregnancy complications (Rajkovic et al 1997), and male infertility (Wong et al 2002), which positions folate as a limiting factor in the evolution of the human species. Finally folate deficiencies have been linked to an array of cancers including those of the colon (Slattery et al 1999), breast (Zhang et al 1999), pancreas (Stolzenberg- Solomon et al 2001), stomach (Fang et al 1997), cervix (Butterworth 1993), bronchus (Kamei et al 1993), and blood (Skibola et al 1999). …”

Section: 10 Folate Deficiencies and Human Diseasementioning

confidence: 99%

Folate in Skin Cancer Prevention

Williams

Jacobson

Kim

et al. 2011

Subcellular Biochemistry

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Skin, the largest, most exposed organ of the body, provides a protective interface between humans and the environment. One of its primary roles is protection against exposure to sunlight, a major source of skin damage where the UV radiation (UVR) component functions as a complete carcinogen. Melanin pigmentation and the evolution of dark skin is an adaptive protective mechanism against high levels of UVR exposure. Recently, the hypothesis that skin pigmentation balances folate preservation and Vitamin D production has emerged. Both micronutrients are essential for reproductive success. Photodegradation of bioactive folates suggests a mechanism for the increased tendency of populations of low melanin pigmentation residing in areas of high UV exposure to develop skin cancers. Folate is proposed as a cancer prevention target for its role in providing precursors for DNA repair and replication, as well as its ability to promote genomic integrity through the generation of methyl groups needed for control of gene expression. The cancer prevention potential of folate has been demonstrated by large-scale epidemiological and nutritional studies indicating that decreased folate status increases the risk of developing certain cancers. While folate deficiency has been extensively documented by analysis of human plasma, folate status within skin has not been widely investigated. Nevertheless, inefficient delivery of micronutrients to skin and photolysis of folate argue that documented folate deficiencies will be present if not exacerbated in skin. Our studies indicate a critical role for folate in skin and the potential to protect sun exposed skin by effective topical delivery as a strategy for cancer prevention.

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“…The one-carbon (1C) metabolism cycle is a network of biochemical reactions that provide 1C units required for critical intracellular processes (Mason 2003). Impairments of the 1C metabolism cycle have increasingly been implicated in numerous disease states including cancer, neurodegenerative disease and adverse reproductive outcomes (Mason 2003;Castro et al 2003;MRC Vitamin Study Research Group 1991;Selhub et al 1995;Malinow et al 1993;Petri et al 1996;Perry et al 1995;Butterworth 1993;Kamei et al 1993;Slattery et al 1999;Zhang et al 1999;Dekker et al 1995;Rajkovic et al 1997;Clarke et al 1998). Disturbances to the cycle may be due to insufficient intakes of dietary cofactors such as folate and other B vitamins as well as common polymorphisms in genes involved in the 1C metabolism cycle.…”

Section: Introductionmentioning

confidence: 99%

Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism

Massey

2013

Genes Nutr

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Genetic and nutritional factors play a role in determining the functionality of the one-carbon (1C) metabolism cycle, a network of biochemical reactions critical to intracellular processes. Genes encoding enzymes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) may determine biomarkers of the cycle including homocysteine (HCY), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). MTHFR C677T is an established genetic determinant of HCY but less is known of its effect on SAM and SAH. Conversely, the relationship between MTR A2756G and HCY remains inconclusive, and its effect on SAM and SAH has only been previously investigated in a female-specific population. Folate and vitamin B12 are essential substrate and cofactor of 1C metabolism; thus, consideration of gene-nutrient interactions may clarify the role of genetic determinants of HCY, SAM and SAH. This cross-sectional study included 570 healthy volunteers from Kingston, Ontario, Ottawa, Ontario and Halifax, Nova Scotia, Canada. Least squares regression was used to examine the effects of MTR and MTHFR polymorphisms on plasma HCY, SAM and SAH concentrations; gene-gene and gene-nutrient interactions were considered with the inclusion of cross-products in the model. Main effects of MTR and MTHFR polymorphisms on HCY concentrations were observed; however, no gene-gene or gene-nutrient interactions were found. No association was observed for SAM. For SAH, interactions between MTR and MTHFR polymorphisms, and MTHFR polymorphism and serum folate were found. The findings of this research provide evidence that HCY and SAH, biomarkers of 1C metabolism, are influenced by genetic and nutritional factors and their interactions.

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Experimental study of the therapeutic effects of folate, vitamin A, and vitamin B12 on squamous metaplasia of the bronchial epithelium

Cited by 28 publications

References 25 publications

Interventional study of high dose folic acid in gastric carcinogenesis in beagles

Interventional study of high dose folic acid in gastric carcinogenesis in beagles

Folate in Skin Cancer Prevention

Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism

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