Arsenic contamination: a potential hazard to the affected areas of West Bengal, India.

Arsenic contamination in groundwater is becoming more and more a worldwide problem. Nearing 50 million of people are at health risk from arsenic contamination at Ganga-Meghna-Bramhaputra basin. The experimental results of the five blocks under Malda district of West Bengal, India, showed that the arsenic concentration in groundwater (0.41-1.01 mg/l) was higher than the permissible limit for drinking water (0.01 mg/l) (WHO) and FAO (Food and Agriculture Organization) permissible limit for irrigation water (0.10 mg/l). The soil arsenic level (13.12 mg/kg) crossed the global average (10.0 mg/kg), but within the maximum acceptable limit for agricultural soil (20.0 mg/kg) recommended by the European Union. The total arsenic concentration on food crops varied from 0.000 to 1.464 mg/kg of dry weight. The highest mean arsenic concentration was found in potato (0.456 mg/kg), followed by rice grain (0.429 mg/kg). The total mean arsenic content (milligrams per kg dry weight) in cereals ranged from 0.121 to 0.429 mg/kg, in pulses and oilseeds ranged from 0.076 to 0.168 mg/kg, in tuber crops ranged from 0.243 to 0.456 mg/kg, in spices ranged from 0.031 to 0.175 mg/kg, in fruits ranged from 0.021 to 0.145 mg/kg and in vegetables ranged from 0.032 to 0.411 mg/kg, respectively. Hence, arsenic accumulation in cereals, pulses, oilseed, vegetables, spices, cole crop and fruits crop might not be safe in future without any sustainable mitigation strategies to avert the potential arsenic toxicity on the human health in the contaminated areas.

Polyglutamylation of the dihydrofolate reductase inhibitor gamma-methylene-10-deazaaminopterin is not essential for antitumor activity.

As part of a continuing program aimed at developing nonpolyglutamylatable inhibitors of dihydrofolate reductase that are less toxic and more specific in their action, we herein report the therapeutic efficacy and toxicity of gamma-methylene-10-deazaaminopterin (MDAM) in athymic nude mice bearing advanced human HCT-8 ileocecal xenografts and its antitumor activity in C57BL/6 x DBA/2 F1 (hereafter called B6D2F1) mice bearing P388 murine leukemia. For the xenograft study, MDAM was administered at the maximum tolerated dose by the following dose schedules: (a) 5-day continuous i.v. infusion at 1.0 mg/kg/day (schedule I); and (b) i.v. push, daily for 5 days at 50 mg/kg/day (schedule II). The maximum tolerated dose values for methotrexate (MTX) under these conditions were 0.2 and 1.0 mg/kg/day for schedule I and schedule II, respectively. MTX did not exhibit any significant antitumor activity in this model system by both schedules; however, MDAM induced complete responses of 13 and 25% and partial responses of 25 and 50% by schedules I and II, respectively. MDAM also exhibited antitumor activity significantly superior to that of MTX in the P388 tumor model. One of the enantiomers of MDAM, which possesses the natural configuration at the gamma-methyleneglutamate moiety (l-MDAM), has been shown to be a better inhibitor of human recombinant dihydrofolate reductase and H35 hepatoma cell growth than D,L-MDAM. L-MDAM inhibited the uptake of radiolabeled folinic acid to H35 hepatoma cells eight times more efficiently than MTX. The results indicate that the superior activity of MDAM relative to MTX may be partially due to a combination of enhanced transport to tumor cells and slower deactivation by aldehyde oxidase.