Cassia senna inhibits mutagenic activities of benzo[a]-pyrene, aflatoxin B1, shamma and methyl methanesulfonate.

Ethanol extract of Senokot tablets (Cassia senna concentrate used as vegetable laxative), was found to be non-mutagenic while it inhibited the mutagenicity of benzo[a]pyrene, shamma, aflatoxin B1 and methyl methanesulfonate in the Ames histidine reversion assay using the Salmonella typhimurium tester strain TA98. While the Senokot extract completely inhibited the mutagenicity of promutagens (i.e. metabolic activation dependent) like benzo[a]pyrene and shamma, it reduced the mutagenic activity of the direct acting mutagen methyl methanesulfonate by only 58%. The mutagen aflatoxin B1 showed a 25-fold increase in the number of histidine revertants per plate at low concentrations (1.0-4.0 micrograms/plate) in the presence of metabolic activation system while at high concentrations (10.0-30.0 micrograms/plate) it proved to be weakly mutagenic (with a 5-fold increase in the number of histidine revertants/plate) without metabolic activation. The Senokot extract completely inhibited the mutagenic effect of low concentrations of aflatoxin B1 in the presence of metabolic activation but not that resulting from higher concentrations without metabolic activation. The results obtained with benzo[a]pyrene, shamma and aflatoxin B1 indicated that the antimutagenic effects of Senokot extract could be largely due to an interaction with the metabolic process involved in the activation of procarcinogens. However, the results obtained with methyl methanesulfonate suggested that factors in Senokot may also interact with direct mutagens to produce some antimutagenic effects. An ethanol extract of crude senna leaves found to be weakly mutagenic also inhibited (though less than Senokot) the mutagenic effect of benzo[a]pyrene suggesting that the antimutagenic principle is present in the complex plant material itself.

Mutagenicity of cisplatin and carboplatin used alone and in combination with four other anticancer drugs.

Mutagenicity of cisplatin and carboplatin was compared by using the drugs alone and in combination with bleomycin, 5-fluorouracil, vincristine and methotrexate in the Ames Salmonella assay employing the tester strains TA98, TA100 (excision deficient) and TA102 (excision proficient). Cisplatin showed the maximum yield of histidine revertants in TA98 and TA100 at 2 micrograms/plate followed by a decrease in the number of mutants/plate with increasing concentrations. In the excision proficient strain TA102, there was no decline in the number of mutants/plate even at a concentration of 8 micrograms/plate. Basically, similar results were also obtained with carboplatin but using higher concentrations of the drug. When cisplatin or carboplatin was combined with other anticancer drugs, there was no differential modification of mutagenicity of the 2 platinum compounds in any of the bacterial tester strains.

Mutagenic and antimutagenic factor(s) extracted from a desert mushroom using different solvents.

A desert mushroom called Al-faga (Tirmania pinoyi) was sequentially extracted with boiling water, chloroform and ethanol under reflux conditions. The water extract was freeze-dried while the organic solvents were fully evaporated to obtain residues, which were redissolved in dimethylsulphoxide and then tested for mutagenicity in the Ames assay using the Salmonella tester strains TA98 and TA100. The aqueous extract failed to show any mutagenic activity while the chloroform extract proved to be mutagenic with and without metabolic activation. The ethanol extract was not mutagenic in the same tests. However, ethanol extract combined with known carcinogens like benzo[a]pyrene or 7,12-dimethyl-benz[a]anthracene (with metabolic activation) inhibited the carcinogen-induced mutagenicity in a dose-dependent manner. These results show that both mutagens and antimutagens may be extracted from a single food item by using different solvents.

DNA strand breaks and mutations caused by penbutolol, a beta blocker.

Sixteen beta-adrenergic receptor blockers were screened for their mutagenic potential using Salmonella typhimurium strains TA98 and TA100. All except penbutolol were found to be nonmutagenic. Penbutolol was cytotoxic to human fibroblasts and Chinese hamster V79 cells. These effects could be due to its ability to induce DNA-strand breaks detected by hydroxyapatite chromatography, which remained unrepaired within 1 h of incubation. Under the same conditions strand-breaking activity of propranolol, timolol and indenolol could not be detected. Three potential impurities of penbutolol were ineffective in causing DNA-strand breakage and one metabolite of this drug was found to be nonmutagenic.

Inhibition of DNA and protein synthesis and cell division by photoactivated haematoporphyrin derivative in hamster ovary cells.

Experiments were performed on cultured Chinese hamster ovary cells exposed to haematoporphyrin derivative (HpD) plus light, yielding survival rates of 40-100%. [3H]-thymidine, [3H]-tryptophan and [14C]-lysine incorporation were used to quantitate DNA and protein synthesis in surviving cells after exposure. Multiple experiments demonstrated 78% reduction in DNA synthesis during the first day after exposure to 20 micrograms ml-1 HpD plus 1140 Jm-2 light followed by progressive recovery to the normal rate after 4-6 days. Protein synthesis was somewhat less sensitive dropping by 54% initially and fully recovering by day 4. Although this cell line has a normal cycle time averaging approximately 15 h, cell division was rarely observed among lone surviving cells until 72 h after exposure. No inhibition was observed in cells exposed to HpD in the dark. These results indicate that photoactivated HpD has a wide spectrum of reversible nuclear and cytoplasmic effects even at sublethal doses. This is consistent with the notion that clinical photodynamic therapy is not likely to result in chronic morbidity.