Mutagenic activity in bacteria

Aristolochic acid I and aristolochic acid II are mutagenic in several test systems. A mixture of these two compounds was so highly carcinogenic in rats that even homeopathic Aristolochia dilutions have been banned from the German market. The closely related aristolac-tam I and aristolactam II have not been submitted to carcinogenicity testing, but these compounds similarly show mutagenic activity in bacteria. 

Several of the Brassicaceae contain allyl isothiocyanate, which is a potent irritant and has mutagenic activity in bacteria and fetotoxic and carcinogenic effects in rats. However, as allyl isothiocyanate also occurs in ordinary mustard, it would not be realistic to ban aU botanical drugs that contain it, since they commonly provide no more than a normal daily dose of mustard (for example 5 mg of allyl isothiocyanate per 5 g of mustard). 

Safrole is a mutagenic and animal carcinogenic monoterpenoid. It is the major component of oil of sassafras, and lesser quantities occur in essential oils from cinnamon, mace, nutmeg, and star anise. Some of its known or possible metabolites have mutagenic activity in bacteria and it has weak hepatocarcinogenic effects in rodents. Experiments in mice have suggested the possibility of transplacental and lactational carcinogenesis. 

Crude oil did not increase the number of sister chromatid exchanges in cultured human lymphocytes. However, in studies of mice treated in vivo crude oil did cause an increase in the number of sister chromatid exchanges at the highest dose tested. No effects were observed in bone-marrow cells or sperm. Sister chromatid exchanges were caused by the aromatic fraction of crude oil in cultured mammalian cells. Crude oil extracts did not induce mutation in bacteria. However, the neutral fractions of crude oil which contain aromatic or polycyclic aromatic compounds generally had mutagenic activity in bacteria. 

Genotoxicity. 1,2-Dibromoethane has been tested for mutagenic activity in a battery of in vitro and in vivo assay systems. It is mutagenic in bacteria, fungi, fruit flies, and cultured mammalian cells (Ames andYanofasky 1971 Barber 1981 Brimeret al. 1982 Crespi etal. 1985 Moriya etal. 1983 ... 

Malonaldehyde induced mutation in bacteria that were either DNA repair competent or were sensitive to oxidative DNA damage. It had been suggested previously that all or part of the activity might be attributable to impurities, which occur as a result of malonaldehyde instability. However, specially purified or specially synthesized malonaldehyde continued to show mutagenic activity in A typhimurium his D3052 (Basu Mamett, 1983). 

Probably the major point of interest with this compound at the present time is its carcinogenic potential in humans. Metronidazole, in common with other members of the imidazole group, has been shown to increase mutation rates in bacteria in vitro (28 ). Niridazole was found in these tests to be mutagenically active at a much lower concentration than metronidazole. Both of these compounds also showed mutagenic activity in the host-mediated assay test in mice. 

Shigaeva MK, Savitskaya IS. 1981. Comparative study of the mutagenic activity of some organophosphoms insecticides in bacteria. Tsitol Genet 15 68-72. 

The Ames test involves the reversion from a his— to his+ phenotype in any one of multiple bacterial strains (usually five strains are tested simultaneously). If the addition of test compound to a his— strain of bacteria allows them to grow on histidine deficient media, the obvious conclusion is compound-induced mutagenesis and a high potential hazard for the compound being carcinogenic. This test can also be conducted in the presence or absence of metabolic activation, in order to provide more information on potential risks (i.e., the parent compound may not be mutagenic, but the primary metabolite may present a safety risk). In practice, a positive Ames test almost always leads to discontinuing work on a compound of interest, and so these data are always collected prior to nomination of a compound for development. 

NishiokaH. 1975. Mutagenic activities of metal compounds in bacteria. MutRes 31 185-189. 

Principe et al. 1981 Rosenkranz 1977). The mutagenicity of 1,2-dibromoethane in bacteria was not influenced by mammalian metabolizing systems in four out of five studies (Barber et al. 1981 Moriya et al. 1983 Principe et al. 1981 Stolzenberg and Mine 1980). However, detection of its mutagenic activity is influenced by the amount of glutathione present (Kerklaan et al. 1985 Zoetemelk et al. 

This herb has been part of folk medicine since pre-Christian times (247). It has been primarily used as a sedative and for the treatment of epilepsy. Consistent with this use, this herb reportedly can increase synaptic concentrations of GABA (248). GABA has also been isolated from Valeria and extracts of Valeria have been reported to bind to GABA receptors in rat brain. Although Valeria has been reported to be active in rodent models of depression, there have been no efficacy trials in humans. The potential adverse effects of Valeria include the sensation of strangeness ( 247) and several cases of liver damage (e.g., central lobular necrosis) (249). Mutagenicity in bacteria has been reported and attributed to unstable, water-insoluble valepotriates ( 238). As a result of these reports, many, but not all, commercial preparations of Valeria use water-soluble extracts standardized for their content of valeric acid. 

Propanc sultone is mutagenic in bacteria. It is positive for many genetic activity end-points in vitro in rodent and human cells. 1,3-Propane sultone induces DNA strand breaks in vivo in rat brain cells. 

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