In vitro inhibition of food borne mutagens induced mutagenicity by cinnamon (Cinnamomum cassia) bark extract.

Cinnamon (Cinnamomum cassia) is an important spice which is widely consumed in the Indian subcontinent as well as in several other parts of the world. In the present study, NMR spectroscopy showed the presence of cinnamaldehyde to be the major component of the bark. The possible mutagenic effects of cinnamon bark ethanolic extract (CEE, 0.01-1 mg/plate) cinnamon oil (CNO, 0.125-1 mg/plate), and its active component cinnamadehyde (CLD, 0.125-1 mg/plate) were evaluated. Antimutagenic activity of CEE, CNO, and CLD was also tested against various food borne mutagens (heterocyclic amines and aflatoxin B1 (AFB1)) and sodium azide (SA) using Ames assay. Similarly, the antimicrobial activity was studied using agar well diffusion assay against various pathogens. CEE was non-mutagenic in any of the five tester strains of Salmonella typhimurium (TA97a, TA98, TA100, TA102, and TA104) in Ames test. CEE exhibited antimutagenic activity against all the mutagens tested in the higher doses. Additionally, CEE, CNO, and CLD were effective against various pathogens such as Staphylococcus aureus, Proteus vulgaris, S. typhimurium, Klebsiella pneumoniae, and Escherichia coli in the agar well diffusion assay. Promising antimutagenic and antimicrobial properties were shown by the cinnamon bark ethanolic extract and cinnamaldehyde, respectively. Therefore, their role in cancer chemoprevention, as well as a natural antimicrobial agent must be exploited and studied in depth in in vivo conditions.

Mutagenicity and antimutagenicity studies of DRDE-07 and its analogs against sulfur mustard in the in vitro Ames Salmonella/microsome assay.

Sulfur mustard (bis(2-chloroethyl) sulfide, SM), a chemical warfare agent, is classified as a class I human carcinogen by IARC. No effective antidote against this agent is available. The synthetic aminothiol, amifostine, earlier known as WR-2721, has been extensively used as a chemical radioprotector for normal tissues in cancer radiotherapy and chemotherapy. SM is a radiomimetic agent; this prompted us to evaluate the protective efficacy of amifostine and three of its analogs, DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulphide], DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide] and DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide], against sulfur mustard-induced mutagenicity in the Ames Salmonella/microsome assay. The antidotes were also evaluated for possible mutagenic activity. DRDE-07 was mutagenic in strain TA104 in the absence of S9; DRDE-30 was mutagenic in strain TA100; amifostine and DRDE-35 did not show mutagenic activity in any of the five tester strains used. SM is mutagenic in strains TA97a and TA102, with or without S9 activation. In the antimutagenicity studies, DRDE-07 and DRDE-35 showed promising antimutagenic activity against SM in the absence of S9, in comparison to amifostine. DRDE-07 and DRDE-35 are promising protective agents against SM-induced mutagenicity.

Inhibitory effects of neem seed oil and its extract on various direct acting and activation-dependant mutagens-induced bacterial mutagenesis.

CONTEXT: Azadirachta indica A. Juss (Meliaceae), commonly called neem is a plant native to the Indian sub-continent. Neem oil extracted from the seeds of neem tree has shown promising medicinal properties. OBJECTIVE: To investigate the possible anti-mutagenic activity of neem seed oil (NO) and its dimethylsulfoxide (DMSO) extract (NDE) on the mutagenicity induced by various direct acting and activation-dependant mutagens. MATERIALS AND METHODS: The possible anti-mutagenic activity of NO (100-10,000 µg/plate) and NDE (0.1-1000 µg/plate) as well as the mechanism of anti-mutagenic activity was studied in an in vitro Ames Salmonella/microsome assay. RESULTS: NSO and NDE inhibited the mutagenic activity of methyl glyoxal (MG), in which case the extent of inhibition ranged from 65 to 77% and against 4-nitroquinoline-N-oxide (NQNO); it showed a 48-87% inhibition in the non-toxic doses. Similar response of NSO and NDE was seen against the activation-dependant mutagens aflatoxin B1 (AFB1, 48-88%), benzo(a)pyrene (B(a)P, 31-85%), cyclophosphamide (CP, 66-71%), 20-methylcholanthrane (20-MC, 37-83%) and acridine orange (AO, 39-72%) in the non-toxic doses. Mechanism-based studies indicated that NDE exhibits better anti-mutagenic activity in the pre- and simultaneous-treatment protocol against MG, suggesting that one or several active phytochemicals present in the extract covalently bind with the mutagen and prevent its interaction with the genome. DISCUSSION AND CONCLUSION: These findings demonstrate that neem oil is capable of attenuating the mutagenic activity of various direct acting and activation-dependant mutagens.

Genotoxicity assessment of NIM-76 and its formulation (pessary) in an in vitro Ames Salmonella/microsome assay and in vivo mouse bone marrow micronucleus test.

The possible genotoxic potential of NIM-76, a volatile fraction obtained from neem oil, having promising contraceptive activity, as well as its formulation product, called pessary (7.5% NIM-76 in polyethylene glycol), were evaluated in the Ames assay and mouse bone marrow micronucleus (MN) assay. Genotoxicity of NIM-76 (0.1-1000 µg/plate) and pessary (0.1-10,000 µg/plate) were studied using the liquid preincubation protocol of the Ames assay both in the presence and absence of S9. Likewise, the ability of NIM-76 [1-1000 mg/kg body weight (b.w.)] and its formulation product (18.75-300 mg/kg b.w.) to induce clastogenic effects were studied in the female mouse bone marrow MN test by using a two-dose intraperitoneal treatment protocol. There was no increase in the number of revertant colonies resulting from NIM-76 or pessary at any of their doses over the respective negative control plates, either in the presence or absence of S9. Similarly, in the MN assay, neither of them showed any clastogenic activity because there was no significant increase in the frequency of micronucleated polychromatic erythrocytes, over the negative control group of animals. The use of this compound in humans is therefore not likely to have mutagenic effects and may be considered as safe with regard to genotoxic potential.