The Detection of DNA Adducts (Risk Factors for DNA Damage). A Method for Genomic DNA, the Results and Some Effects of Nutritional Intervention

 
J. Nutr. & Env. Medicine. 2002; 12: 19-31

McLaren Howard, John, Biolab Medical Unit, 9 Weymouth Street, London W1W 6DB, UK

Abstract

Purpose: Detection of organic chemical and metal DNA adducts in clinical samples.

Design: Open comparison between controls, people having routine laboratory investigations and groups of people with known exposure to toxic chemicals/metals.

Materials and Methods: Using genomic DNA from peripheral blood leucocytes, organic chemical DNA adducts were group separated by gas-liquid chromatography and metal DNA adducts were identified by plasma emission spectrography and spectrophotometry. There were 12 controls, 54 people having routine laboratory investigations, 14 tobacco smokers, seven people with known pesticide exposure, five with known toxic and metal exposure, one person exposed to mycotoxins and two people with known nickel sensitivity. Eight of the participants with positive findings were re-tested after nutritional intervention.

Results: The previous finding of nitrosamine adducts in smokers is confirmed (13 of 14 smokers). Nitrosamine adducts were also found in nine non-smokers. DNA adducts were found to halogenated phenols (10), halogenated benzenes (10), vinyl halides (1), aldehydes (1), chloroethylenes (2), aflatoxin/mycotoxins (5), malondialdehyde (22) and lindane (3). The lindane DNA adduct is a new finding. Seven unidentified adducts were found. Adducts were found to lead (9), cadmium (20), mercury (7), aluminium (1), antimony (4), arsenic (8), nickel (20), strontium (1), copper (1), manganese (4), chromium (1) and cobalt (1). Two of the controls had low-level adducts. In eight people,3 months of nutritional intervention led to the elimination of some DNA adducts and a semi-quantitiative reduction in the level of others.

Conclusions: Significant numbers of DNA adducts can be detected in clinically relevant blood samples. In smokers, the expected nitrosamine adducts are accompanied by cadmium DNA and nickel DNA adducts. Nickel DNA adducts were found in some non-smokers and nickel is a known carcinogen. Lindane DNA adducts are identified for the first time. The results link gene research with the nutritional and environmental approaches to medicine. Early indications are that the burden of DNA adducts may be reduced by nutritional intervention.

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