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Nutriomes and nutrient arrays - the key to personalised nutrition for DNA damage prevention and cancer growth control.

Fenech MF - Genome Integr (2010)

Bottom Line: DNA damage at the base-sequence, epigenome and chromosome level is a fundamental cause of developmental and degenerative diseases.The challenge is to identify for each individual the combination of micronutrients and their doses (i.e. the nutriome) that optimises genome stability and DNA repair.In this paper I describe and propose the use of high-throughput nutrient array systems with high content analysis diagnostics of DNA damage, cell death and cell growth for defining, on an individual basis, the optimal nutriome for DNA damage prevention and cancer growth control.

View Article: PubMed Central - HTML - PubMed

Affiliation: CSIRO Food and Nutritional Sciences, PO Box 10041 Adelaide BC, SA, 5000, Australia. michael.fenech@csiro.au.

ABSTRACT
DNA damage at the base-sequence, epigenome and chromosome level is a fundamental cause of developmental and degenerative diseases. Multiple micronutrients and their interactions with the inherited and/or acquired genome determine DNA damage and genomic instability rates. The challenge is to identify for each individual the combination of micronutrients and their doses (i.e. the nutriome) that optimises genome stability and DNA repair. In this paper I describe and propose the use of high-throughput nutrient array systems with high content analysis diagnostics of DNA damage, cell death and cell growth for defining, on an individual basis, the optimal nutriome for DNA damage prevention and cancer growth control.

No MeSH data available.


Related in: MedlinePlus

High riboflavin tends to increase genome instability when folate status is low. Folate-riboflavin interactive effects on CBMNcyt assay DNA damage biomarkers. It is evident from these results that folate deficiency tends to increase micronuclei, nucleoplasmic bridges and nuclear buds and these effects are further aggravated by high riboflavin in a low folic acid background. For more details refer to Kimura et al 2004 [28]. L, low; H, high; F, folic acid; R, riboflavin.
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Figure 3: High riboflavin tends to increase genome instability when folate status is low. Folate-riboflavin interactive effects on CBMNcyt assay DNA damage biomarkers. It is evident from these results that folate deficiency tends to increase micronuclei, nucleoplasmic bridges and nuclear buds and these effects are further aggravated by high riboflavin in a low folic acid background. For more details refer to Kimura et al 2004 [28]. L, low; H, high; F, folic acid; R, riboflavin.

Mentions: Such a system would also identify the deficiency and safe upper limit range for that individual for multiple micronutrients within a single scan and identify any unexpected combinations that could prove counter-intuitively cytotoxic or genotoxic. The plausibility of such a possibility is supported by our observation that genome instability increased under low folate conditions (20 nM) if riboflavin concentration was increased to replete status [28] (figures 2, 3, 4, 5) possibly because the latter, which is the precursor of the FAD cofactor for MTHFR, increases MTHFR activity which catalyses the irreversible conversion of 5,10methylenetetrahydrofolate to 5-methyltetrahydrofolate making the former folate species less bioavailable for dTMP synthesis from dUMP and thus increasing uracil in DNA. Excessive uracil in DNA causes abasic sites and DNA strand breaks when uracil glycosylases attempt to repair this highly mutagenic lesion [35,41,42]. Therefore it is important to develop a nutrient array system that can efficiently interrogate multiple micronutrient combinations at different dosages. This type of approach has the added advantage that it becomes possible to identify an individual's nutriome for genome health maintenance without needing to know the person's genetic background. Furthermore, such systems could also be used to compare the response of different genotypes under the same nutriome conditions and estimate the percentage of the variance of the biomarkers measured that are explained by different genotype and different nutrients in the nutriomes tested including their interactions (see figures 2, 3, 4, 5 as an example for the effects of the MTHFR C677T genotype relative to folic acid and riboflavin on DNA damage, homocysteine and cell growth biomarkers).


Nutriomes and nutrient arrays - the key to personalised nutrition for DNA damage prevention and cancer growth control.

Fenech MF - Genome Integr (2010)

High riboflavin tends to increase genome instability when folate status is low. Folate-riboflavin interactive effects on CBMNcyt assay DNA damage biomarkers. It is evident from these results that folate deficiency tends to increase micronuclei, nucleoplasmic bridges and nuclear buds and these effects are further aggravated by high riboflavin in a low folic acid background. For more details refer to Kimura et al 2004 [28]. L, low; H, high; F, folic acid; R, riboflavin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927499&req=5

Figure 3: High riboflavin tends to increase genome instability when folate status is low. Folate-riboflavin interactive effects on CBMNcyt assay DNA damage biomarkers. It is evident from these results that folate deficiency tends to increase micronuclei, nucleoplasmic bridges and nuclear buds and these effects are further aggravated by high riboflavin in a low folic acid background. For more details refer to Kimura et al 2004 [28]. L, low; H, high; F, folic acid; R, riboflavin.
Mentions: Such a system would also identify the deficiency and safe upper limit range for that individual for multiple micronutrients within a single scan and identify any unexpected combinations that could prove counter-intuitively cytotoxic or genotoxic. The plausibility of such a possibility is supported by our observation that genome instability increased under low folate conditions (20 nM) if riboflavin concentration was increased to replete status [28] (figures 2, 3, 4, 5) possibly because the latter, which is the precursor of the FAD cofactor for MTHFR, increases MTHFR activity which catalyses the irreversible conversion of 5,10methylenetetrahydrofolate to 5-methyltetrahydrofolate making the former folate species less bioavailable for dTMP synthesis from dUMP and thus increasing uracil in DNA. Excessive uracil in DNA causes abasic sites and DNA strand breaks when uracil glycosylases attempt to repair this highly mutagenic lesion [35,41,42]. Therefore it is important to develop a nutrient array system that can efficiently interrogate multiple micronutrient combinations at different dosages. This type of approach has the added advantage that it becomes possible to identify an individual's nutriome for genome health maintenance without needing to know the person's genetic background. Furthermore, such systems could also be used to compare the response of different genotypes under the same nutriome conditions and estimate the percentage of the variance of the biomarkers measured that are explained by different genotype and different nutrients in the nutriomes tested including their interactions (see figures 2, 3, 4, 5 as an example for the effects of the MTHFR C677T genotype relative to folic acid and riboflavin on DNA damage, homocysteine and cell growth biomarkers).

Bottom Line: DNA damage at the base-sequence, epigenome and chromosome level is a fundamental cause of developmental and degenerative diseases.The challenge is to identify for each individual the combination of micronutrients and their doses (i.e. the nutriome) that optimises genome stability and DNA repair.In this paper I describe and propose the use of high-throughput nutrient array systems with high content analysis diagnostics of DNA damage, cell death and cell growth for defining, on an individual basis, the optimal nutriome for DNA damage prevention and cancer growth control.

View Article: PubMed Central - HTML - PubMed

Affiliation: CSIRO Food and Nutritional Sciences, PO Box 10041 Adelaide BC, SA, 5000, Australia. michael.fenech@csiro.au.

ABSTRACT
DNA damage at the base-sequence, epigenome and chromosome level is a fundamental cause of developmental and degenerative diseases. Multiple micronutrients and their interactions with the inherited and/or acquired genome determine DNA damage and genomic instability rates. The challenge is to identify for each individual the combination of micronutrients and their doses (i.e. the nutriome) that optimises genome stability and DNA repair. In this paper I describe and propose the use of high-throughput nutrient array systems with high content analysis diagnostics of DNA damage, cell death and cell growth for defining, on an individual basis, the optimal nutriome for DNA damage prevention and cancer growth control.

No MeSH data available.


Related in: MedlinePlus