|MILNER, JOHN - NATIONAL CANCER INSTITUTE (NCI, NIH)
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2012
Publication Date: 8/16/2012
Citation: Charron, C.S., Clevidence, B.A., Albaugh, G.P., Milner, J., Novotny Dura, J. 2012. Assessment of DNA damage and repair in adults consuming allyl isothiocyanate or Brassica vegetables. Journal of Nutritional Biochemistry. 24:894-902.
Interpretive Summary: Allyl isothiocyanate (AITC) is a dietary component with potentially important anti-cancer effects. AITC is derived from a compound found in some Brassica vegetables, including cabbage, mustard, Brussels sprouts, kale, and cauliflower. Also known as mustard oil, AITC is additionally found in the food supply as a food additive, giving a pungeant flavor to mayonnaise products, horseradish spreads, salad dressings, and other spreads and sauces. There is a substantial body of evidence suggesting that components of Brassica vegetables have anticarcinogenic activities, though much of the information about AITC and cancer processes has been obtained from cell studies. To investigate the potential of dietary AITC to influence DNA integrity and repair, we have conducted a human feeding study in which volunteers consumed AITC or cabbage and mustard (both of which contained AITC), then provided blood and urine samples for assessment of DNA damage and repair. Study volunteers were evaluated for genotype for three genes with potential to influence the study results. It was found that consumption of AITC caused DNA strand breaks in the short term, but these breaks disappeared quickly. Since DNA repair was not observed, it is not clear if the disappearance of the DNA damage marked removal of damaged cells from the system or if unmonitored DNA repair took place. These results highlight the complexity of the role of Brassica vegetables in cancer development. These results will be used by scientists studying diet and cancer prevention.
Technical Abstract: Allyl isothiocyanate (AITC) is a dietary component with potentially important anti-cancer effects, though much of the information about AITC and cancer processes has been obtained from cell studies. To investigate the effect of AITC on DNA integrity and repair in vivo, a human feeding study was conducted. Healthy adults (n=46) consumed AITC, AITC-rich vegetable products (pureed cabbage plus mustard), or a control mayonnaise spread as part of a controlled diet for 10 days in a crossover design. On the eleventh morning, volunteers provided fasting blood and urine samples, then consumed treatments and provided additional blood and urine samples at 3 and 6 hours post consumption. Study volunteers were evaluated for genotype for deletions in glutathione S-transferase genes GSTM1 and GSTT1 and single nucleotide polymorphisms in DNA repair gene XPD (codons 321 and 751). Peripheral blood mononuclear cells (PBMCs) were isolated and DNA integrity was assessed by single cell gel electrophoresis. Urine samples were analyzed for 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) and creatinine. Ten day intake of neither AITC nor cabbage/mustard affected DNA strand breaks in PBMCs or urinary 8-oxodG. Acute intake of both AITC and cabbage/mustard increased DNA strand breaks 3 h post-consumption, and this difference disappeared at 6 h. Genotypes for GSTM1, GSTT1, and XPD were not associated with outcome variables. In summary, DNA damage appeared to be induced in the short term by AITC and AITC-rich products, but that damage disappeared quickly, and neither AITC nor AITC-rich products affected DNA base excision repair.