-Food security, nutritional quality and safety vary widely around the world. Reaching these three goals is one of the major challenges for the near future. Up to now, industrialized production methods have clearly shown severe limitations such as a worldwide contamination of the food chain and water by persistent pesticide residues, and reduced nutrient and flavor contents through low-cost intensive food production and/or processing. In line with several published literature reviews, the French Agency for Food Safety (AFSSA) performed under my coordination an up-to-date exhaustive and critical evaluation of the nutritional and sanitary quality of organic food. This review is based on the AFSSA report issued and recently published studies. The major points are: 1/ organic plant products contain more dry matter and minerals (Fe, Mg); and contain more anti-oxidant micronutrients such as phenols and salicylic acid, 2/ organic animal products contain more polyunsaturated fatty acids, 3/ data on carbohydrate, protein and vitamin levels are insufficiently documented, 4/ 94-100% of organic food does not contain any pesticide residues, 5/ organic vegetables contain far less nitrates, about 50% less; and 6/ organic cereals contain overall similar levels of mycotoxins as conventional ones. Thus, organic agricultural systems have already proved able to produce food with high quality standards. I propose also improvements of organic production to achieve sustainable food production for humans in the near future. sustainable agriculture / organic agriculture / human food / nutrition / food safety / contaminants / health

Temozolomide, an oral DNA methylator that inactivates the DNA repair enzyme O 6 -alkylguanine-DNA alkyltransferase (AGAT), has demonstrated anticancer activity on protracted schedules. Protracted schedules may lead to an 'autoenhancement' of temozolomide's inherent cytotoxic potential by cumulative reduction of the cell's capacity for AGAT-mediated DNA repair and resistance. This study was undertaken to characterise AGAT inactivation and regeneration in the peripheral blood mononuclear cells (PBMCs) of patients treated on two protracted temozolomide schedules. O 6 -alkyl guanine-DNA alkyltransferase activity was measured in the PBMCs of patients treated on two phase I protracted temozolomide studies. Patients were treated daily for either 7 days every 2 weeks (Schedule A) or 21 days every 4 weeks (Schedule B). The effects of various temozolomide doses (75 -175 mg m À2 ), treatment duration (7 -21 days), and temozolomide plasma levels on AGAT inactivation and regeneration, as well as the relation between AGAT inactivation and toxicity, were studied. O 6 -alkyl guanine-DNA alkyltransferase activity in PBMCs was measured serially in 52 patients. Marked inactivation of AGAT occurred following 7 days of temozolomide treatment, with mean AGAT activity decreasing by 72% (Po0.0001). Similarly, mean AGAT activity decreased by 63 and 73% after 14 and 21 days of treatment, respectively (Po0.001 for both comparisons). O 6 -alkyl guanine-DNA alkyltransferase inactivation was greater after 7 days of treatment with higher doses of temozolomide than lower doses and remained markedly reduced 7 days post-treatment. However, AGAT inactivation following temozolomide treatment for 14 and 21 days was similar at all doses. On the continuous 21-day schedule, AGAT inactivation was significantly greater in patients who experienced severe thrombocytopenia than those who did not (90.375.5 vs 72.5716.1%, Po0.045). In Conclusion, protracted administration of temozolomide, even at relatively low daily doses, leads to significant and prolonged depletion of AGAT activity, which may enhance the antitumour activity of the agent.

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