Antimutagenic evaluation of vitamins B1, B6 and B12 in vitro and in vivo, with the Ames test.

The aim of this work is to evaluate vitamins B antimutagenic effect against alkylatings methyl-N-nitro-N-nitrosoguanidine (MNNG), ethyl-N-nitro-N'- nitrosoguanidine (ENNG), frameshift mutagens 2-aminoanthracene (2AA) and 2-acetyl-amino-fluorene (2AF) and ROS-generating antibiotics norfloxacin (NOR) and nalidixic acid (NLX), using the in vitro Ames test. In vivo antimutagenesis studies were performed against urinary mutagens induced by NOR (70 mg/kg) or NLX (100 mg/kg) in CD1 mice. Vitamin B1 was antimutagenic against alkylatings MNNG (P<0.05) or ENNG (P<0.001). In fact as per the results observed during the current study, none of the vitamins reduced mutagenesis caused by frameshift mutagens. All of them reduced mutagenesis of NOR or NLX (P<0.001). In vivo studies showed that vitamins B1 and B6 (10 or 100 mg/kg) reduced urinary mutagens from NOR (P<0.001) or NLX (P<0.02) either free or ß-glucoronidase-conjugates. None of the studied samples were toxic for the employed antimutagenic system. Vitamin B12 (4 mg/kg) reduced urinary mutagens of NOR or NLX (P<0.02). Vitamins B inhibited DNA mutations induced by ROS generated by NLX or NOR, both in vitro and in vivo. Vitamin B1is antimutagenic against mutations induced by the alkylating MNNG or ENNG. Based on the observations, employment of vitamins B in vivo can be a promising alternative to reduce genotoxic risk exposure to ROS.

N-methyl-N'-nitroguanidine: irritation, sensitization, and acute oral toxicity, genotoxicity, and methods for analysis in biological samples.

Currently, N-methyl-N'-nitroguanidine (MNG) is being considered by the U.S. Air Force Armament Laboratory for use in explosive formulations. A mammalian toxicity profile has been performed which includes the analysis of chemical impurities and an assessment of the potential for the metabolism of MNG to 1-methyl-3-nitro-1-nitrosoguanidine (MNNG). Potential in situ gastric conversion of MNG to MNNG is a toxicological concern because MNNG is both mutagenic and carcinogenic. The compound was also evaluated in several bioassays to assess its potential genotoxic activity. The acute oral toxicity was determined in male and female Fischer 344 rats administered a single dose of MNG in corn oil. The maximum suspension of MNG that could be delivered, 1 mg MNG/kg body weight, produced no signs of toxic stress during the 14-day observation period. The primary eye and skin irritation potential of MNG was determined in female New Zealand white rabbits using the Draize technique. MNG produced no irritation to intact skin but did produce mild conjunctival irritation. The response of a single guinea pig to the dermal sensitization evaluation indicated that MNG is a weak sensitizer. The results of three genetic tests indicated that MNG does not interact with genetic material. Gastric contents and feces from treated animals showed no evidence of conversion of MNG to MNNG.