Mutagenicity other compounds

Figure 1. Oxidation and other reactions of dialiate and triallate indicating mutagenic activities of the products in the S. typhimurium TA 100 assay (revertants/ nanomole without activation/with activation / designates no data available). 2-Chloroacrolein is a dialiate metabolite in the mouse liver microsome-NADPH system. Dichloroallylsulfonic acid is a urinary metabolite of dialiate. The other compounds are potential metabolites of the respective thiocarbamates. The thio-carbamate sulfoxides are unstable at 25°C.

EhrENBERG, L. (1979). Risk assessment of ethylene oxide and other compounds in Banbury Report 1, page 157 in Assessing Chemical Mutagens The Risk to Humans, McElheny, V.K. AND Abramson, S., Eds. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New Ifork). 

Although it appears that PBBs are not mutagenic, due to their enzyme induction properties, they may potentiate the genotoxic activity of other compounds by activation to reactive intermediates. 

HPLC Fractionation of Extracts of Treated Water. Capillary GC-MS analysis of the XAD-2/ethyl ether extracts of water sampled before and after final chlorination showed no significant difference that could account for the mutagenic activity observed after chlorination. These results indicate that the mutagenic compounds present in the extracts of drinking water are not readily amenable to analysis by GC-MS. However, the possibility cannot be excluded that the mutagenic compounds were present below the detection limit or that they were masked by other compounds. 

The carcinogenic aflatoxins, which are produced by Aspergillus flavus, may be present in infected peanuts and other foodstuffs.790 Like many other compounds that are carcinogenic or mutagenic, the aflatoxins are not unusually reactive chemically. 

Other compounds have been tested to determine the structural requirements for an effective mutagenic agent. The requirements are as follows ... 

A U. S. National Research Council report concludes that natural and synthetic carcinogens are present in human foods at such low levels that they pose little threat.42 It points out that consuming too many calories as fat, protein, carbohydrates, or ethanol is far more likely to cause cancer than consuming the synthetic or natural chemicals in the diet. However, it also mentions several natural substances linked to increased cancer risk heterocyclic amines formed in the overcooking of meat nitrosoamines, aflatoxins, and other mycotoxins.43 Typical of the heterocyclic amine mutagens are compounds 1.9 and 1.10, the first from fried beef and the second from broiled fish 44... 

Symbols El, antimutagenic effect on IQ (A) and I, that on Trp-p-1 (B). Control means the absence of the test compounds. The abbreviations Meth, Eth, n-Pro, and n-But denote methoxymethylene, ethoxymethylene, n-propoxymethylene, and n-butoxymethylene derivatives of 3-(alkoxy)methylene-2-thioxopyrrolidines shown in Table 5. Salmonella typhimurium TA98 was simultaneously treated with IQ (0.5 pg), Trp-p-1 (0.5 pg), and the test compounds (HMTP 130-520 pg/ml other compounds 500 pg/ml) in the presence of S9-mix for 20 min at 37° C. After 48 h incubation, the bacterial survivors and revert-ants were counted, and ratios of the numbers of revertants against those of the survivors were calculated. The ratio obtained from the control (treated with only IQ or Trp-p-1) is defined as 100% mutagenicity. A statistically significant difference between the control and the treating was determined by t-test ( (p < 0.05) and (p < 0.01). 

Lee CH, Lin RH, Liu SH and Lin-Shiau SY (1998) Effects of germanium oxide and other compounds on phcnylmercury acetate-induced gcnotoxicity in cultured lymphocytes. Environ Mol Mutagen 31 157-162. 

In both assays IQ and Trp-P-2 were very potent. IQ, as was seen in the Ames/Salmonella reversion assay, was more potent than Trp-P-2 (see Table II). It is clear from these data that neither the expression of the genetic damage nor the site that is mutated is specific for one compound in bacteria and the other compound in mammalian cells. Thus, the lack of a potent response of IQ in CHO cells is probably not related to the absence of a hypersensitive DNA sequence, but is more likely due to differences in uptake, transport, or metabolism of the mutagens. 

---