Mutagenic chemicals

Fishbein L. 1979. Potential halogenated industrial carcinogenic and mutagenic chemicals II. Halogenated saturated hydrocarbons. Sci Total Environ 11 163-195. 

Pagano, D.A. and Zeiger, E. (1985). The stability of mutagenic chemicals tested in solution. Environ. Mutagen. 7 293-302. 

The urine of people who are heavy smokers contains mutagenic chemicals, chemicals that cause mutations in biological cells. Bioanalytical laboratories can analyze urine samples for these chemicals, but the samples must be cleaned up first prior to extraction with methylene chloride. The procedure for this cleanup utilizes an open column chromatography. Columns several inches tall and about an inch wide are prepared by packing them with an adsorbing resin that has been treated with methyl alcohol. The urine samples are passed through these columns as part of the sample preparation scheme. 

Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH]... 

Professor Bruce Ames, a biochemist at the University of California at Berkeley is one of the pioneers of this type of short-term testing. The Ames Test, as it is called, is now widely used, typically as one of several short-term tests that constitute a series of tests, or battery. A battery is thought necessary because no single test is adequate to detect all types of genotoxicity. The Ames Test involves the use of mutant strains of a common bacterium. Salmonella typhimurium, that back-mutate to their normal state in the presence of a mutagenic chemical or metabolite. Many other bacterial and mammalian cell systems have been made available for this type of testing. 

Fishbein, L. (1979) Potential halogenated indnstrial carcinogenic and mutagenic chemicals. 111. Alkane halides, alkanols and ethers. Sci. total Environ., 11, 223-257... 

Although the rates of spontaneous mutation are low, they can be greatly increased by mutagenic chemicals (Chapter 27) or by irradiation. It is perfectly practical to measure the rates of both forward and back mutation. When this was done, it was found that certain chemicals, e.g., acridine dyes, induce mutations that undergo reverse mutation at a very much lower frequency than normal. It was eventually shown that these mutations resulted either from deletions of one or more nucleotides from the chain or from insertions of extra nucleotides. Deletion and insertion mutations often result from errors during genetic recombination and repair at times when the DNA chain is broken. 

The mutagenic effects of nitrogen mustard were discovered by Auerbach and Robson in 1940, but their results were not published until 1947 because of the war (Auerbach and Robson, 1947). Lotte Auerbach had been encouraged in the search for mutagenic chemicals by Muller, who felt that this was the road to directed mutation, as opposed to the essentially random nature of mutations induced by X-rays. Robson s role was to help in the handling of the mustard gas, but it seems... 

Ames Test The Ames test, developed by Bruce Ames and his coworkers at the University of California, Berkeley, depends on the ability of mutagenic chemicals to bring about reverse mutations in Salmonella typhimurium strains that have defects in the histidine biosynthesis pathway. These strains will not grow in the absence of histidine but can be caused to mutate back to the wild type, which can synthesize histidine and hence can grow in its absence. The postmitochondrial supernatant (S-9 fraction), obtained from homogenates of livers of rats previously treated with PCBs in order to induce certain cytochrome P450 isoforms, is also included in order to provide the activating enzymes involved in the production of the potent electrophiles often involved in the toxicity of chemicals to animals. 

If this is positive, the chemical is classified as a presumed mammalian mutagen if negative, the chemical is a presumed mammalian nonmutagen. An examination of 36 mutagenic chemicals in which several of these tests had been done showed that at least 31 would have been identified by Tier I tests alone. This suggests that the more expensive Drosophila tests would not be needed for most chemicals. 

That an up-to-date register of mutagenic chemicals be kept and the information be made generally available. 

One possible way to identify hazards and risks is to consider the problem as a sequence of steps. Testing and evaluating potentially mutagenic chemicals could proceed through the following steps ... 

Hazard Characterization. Once chemicals have been identified as mutagens, they can be classified according to their relative potency and spectrum of effects. The activity of mutagenic chemicals varies markedly, as does the nature of the damage they cause. 

Whether and how a mutagenic chemical can be used depend on a number of considerations, some tangible, some not. 

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