Mutagens and carcinogens - AccessScience from McGraw-Hill Education
Research indicates that genes react to environmental cues by way of several different Interestingly, DNA repair pathway genes are often mutated in cancers and other . Discovering the Relationship Between DNA and Protein Production. Most forward mutations (normal gene to mutant form) are recessive the difference for the purposes of thinking about rates in this course) is. Links to Primary Literature; Additional Readings. A mutagen is Although mutagen and carcinogen are not synonymous terms, the ability of a substance to induce mutations and its ability to induce cancer are strongly correlated. Mutagenesis.
Figure Ames test results showing the mutagenicity of aflatoxin B1, which is also a potent carcinogen. The TA strain is highly sensitive to reversion through base-pair more Bacteria are evolutionarily a long way removed from humans. Can the results of a test on bacteria have any real significance in detecting chemicals that are dangerous for humans?
Mutation, Mutagens, and DNA Repair
First, we have seen that the genetic and chemical nature of DNA is identical in all organisms, so a compound acting as a mutagen in one organism is likely to have some mutagenic effects in other organisms. Second, Ames devised a way to simulate the human metabolism in the bacterial system. In mammals, much of the important processing of ingested chemicals takes place in the liver, where externally derived compounds normally are detoxified or broken down.
In some cases, the action of liver enzymes can create a toxic or mutagenic compound from a substance that was not originally dangerous Figure Ames incorporated mammalian liver enzymes in his bacterial test system, using rat livers for this purpose. Figure outlines the procedure used in the Ames test.
Mutagens and carcinogens
Figure The metabolic conversion of benzo a pyrene BP into a mutagen and a carcinogen. Benzo a pyrene goes through several steps a as it is made more water soluble prior to excretion. One of the intermediates in this process, a diol epoxide 3is capable more Figure Summary of the procedure used for the Ames test.
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First, rat liver enzymes are mobilized by injecting the animals with Arochlor. Now, let's look at a couple examples of exogenous mutagens, and there are many different types of exogenous mutagens, but we're really only going to talk about two.
Now, intercalators are one example, and one of them is called ethidium bromide, which you may be familiar with if you've ever done a PCR experiment before, and what ethidium bromide will do is it will jump into a DNA double helix and stick itself between the two strands, and when these intercalators intercalate into DNA, they can deform the structure of the DNA and cause some serious problems. Base analogs, like 5-bromouracil, which we also call 5-BU, pretend to be a certain base, but then act differently than that base normally would.
Mutagen - Wikipedia
So, in the case of 5-BU, it's an analog of uracil and looks a lot like it, but once it's incorporated into DNA, it can shift between two different forms. In its keto-form, it will pair best with adenine.
While it's in enol-form, it will pair best with guanine. Now, if you're familiar with organic chemistry, you might know that 5-BU can convert between its keto and enol form through something called a tautomerization reaction, and overall you can see how this base analog might be able to induce mutations in a DNA strand.
Now, the last thing we're going to talk about is what a carcinogen is. Now, carcinogens can be mutagens, but not all of them are, but in general, you can say that a carcinogen is something that can lead to cancer, which, if you remember, is when cells in an organism divide uncontrollably and can form big masses of cells, called tumors.
Now, some carcinogens will work by making mutations in DNA that lead to cancer, but sometimes they might carry out their effects simply by increasing the rate at which a bunch of cells divide, without actually affecting their DNA, and some examples of carcinogens are tobacco, which come from cigarettes, asbestos, which used to be used as home insulation, and even UV radiation.
Mutagens may therefore be also carcinogens. However, some mutagens exert their mutagenic effect through their metabolites, and therefore whether such mutagens actually become carcinogenic may be dependent on the metabolic processes of an organism, and a compound shown to be mutagenic in one organism may not necessarily be carcinogenic in another.
Powerful mutagens may result in chromosomal instability,  causing chromosomal breakages and rearrangement of the chromosomes such as translocationdeletionand inversion.
Such mutagens are called clastogens. Mutagens may also modify the DNA sequence; the changes in nucleic acid sequences by mutations include substitution of nucleotide base-pairs and insertions and deletions of one or more nucleotides in DNA sequences. Although some of these mutations are lethal or cause serious disease, many have minor effects as they do not result in residue changes that have significant effect on the structure and function of the proteins.
Many mutations are silent mutationscausing no visible effects at all, either because they occur in non-coding or non-functional sequences, or they do not change the amino-acid sequence due to the redundancy of codons.
Some mutagens can cause aneuploidy and change the number of chromosomes in the cell. They are known as aneuploidogens.
Similar results are also obtained in studies with radiations, indicating that there may be no safe threshold for mutagens. However, the no-threshold model is disputed with some arguing for a dose rate dependent threshold for mutagenesis.
More recent approaches with sensitive analytical methods have shown that there may be non-linear or bilinear dose-responses for genotoxic effects, and that the activation of DNA repair pathways can prevent the occurrence of mutation arising from a low dose of mutagen. Some however may act on the replication mechanism and chromosomal partition.