Assessment of DNA damage and repair in adults consuming allyl isothiocyanate or Brassica vegetables

Abstract

Allylisothiocyanate (AITC) is a dietary component with possible anti-cancer effects, though much information about AITC and cancer has been obtained from cell studies. To investigate the effect of AITC on DNA integrity in vivo, a crossover study was conducted. Adults (n=46) consumed AITC, AITC-rich vegetables (mustard and cabbage), or a control treatment with a controlled diet for 10 days each. On day 11, volunteers provided blood and urine before and after consuming treatments. Volunteers were characterized for genotype for GSTM1 and GSTT1 (glutathione S-transferases) and XPD (DNA repair). DNA integrity in peripheral blood mononuclear cells (PBMCs) was assessed by single cell gel electrophoresis. Urine was analyzed for 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) and creatinine. Ten day intake of neither AITC nor mustard/cabbage(M/C) resulted in statistically significant differences in DNA strand breaks (LS mean % DNA in tail ± SEM: 4.8 ± 0.6 for control, 5.7 ± 0.7 for AITC, 5.3 ± 0.6 for M/C) or urinary 8-oxodG (LS mean µg 8-oxodG/g creatinine ± SEM: 2.95 ± 0.09 for control, 2.88 ± 0.09 for AITC, 3.06 ± 0.09 for M/C). Both AITC and M/C increased DNA strand breaks 3h post-consumption (LS mean % DNA in tail ± SEM: 3.2 ± 0.7 for control, 8.3 ± 1.7 for AITC, 8.0 ± 1.7 for M/C), and this difference disappeared at 6h (4.2 ± 0.9 for control, 5.7 ± 1.2 for AITC, 5.5 ± 1.2 for M/C). Genotypes for GSTM1, GSTT1, and XPD were not associated with treatment effects. 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.

Relationship between conversion rate of glucosinolates to isothiocyanates/indoles and genotoxicity of individual parts of Brassica vegetables

“…Similarly, other studies showed that Brassica plants did not affect DNA integrity of mouse cells [67]. Human population studies revealed that high doses of ITC may lead to short-term DNA damage, but this was reversed quickly by DNA base excision repair [68]. In terms of consumer safety, derivatives of indolic neo-GBS that form DNA adducts with high efficiency, should in longterm perspective be avoided, at least until their safety is not unequivocally confirmed.…”

“…acephala) did not induce DNA strand breaks in mouse cells, neither was genotoxic [67]. Human studies showed that ITC and ITC-rich products induced DNA damage upon shortterm treatment, but that damage disappeared quickly and without affecting DNA base excision repair [68].…”

Comparison of the effect of raw and blanched‐frozen broccoli on DNA damage in colonocytes

“…Scaled for body weight, the daily intake of Brussels sprouts was similar to the intake of broccoli in the present study (25·6 vs 17·3 g kg −1 body weight). In a recent human study, Charron et al . reported a transient increase in DNA damage in peripheral blood mononuclear cells isolated from individuals 3 h after they had consumed either isolated allyl isothiocyanate (114·7 µmol) incorporated into mayonnaise or a mustard/cabbage treatment (150 g of raw homogenized cabbage plus 30 g of Grey Poupon Country Dijon Mustard).…”

“…Scaled for body weight, the daily intake of Brussels sprouts was similar to the intake of broccoli in the present study (25·6 vs 17·3 g kg À1 body weight). In a recent human study, Charron et al 56 reported a transient increase in DNA damage in peripheral blood mononuclear cells isolated from individuals 3 h after they had consumed either isolated allyl isothiocyanate (114·7 μmol) incorporated into mayonnaise or a mustard/cabbage treatment (150 g of raw homogenized cabbage plus 30 g of Grey Poupon Country Dijon Mustard). In contrast, the majority of studies in humans have reported that modest intakes of raw and cooked cruciferous vegetables (85-300 g day À1 ) protect lymphocytes from DNA damage or reduce the urinary excretion of 8-oxo-dG 57-62 (a possible marker of whole body oxidative stress).…”

Mechanisms of the Anticancer Effects of Isothiocyanates

“…AITC, when provided in diet, exhibited short-term reversible DNA damage [101]. This may explain the anticancer effects exerted by AITC, as cancer cells are more susceptible to DNA damage mediated induction of apoptosis.…”