Mutagens and carcinogens
Mutagens and carcinogens
A mutagen is a substance or agent that induces heritable change in cells or organisms. A carcinogen is a substance that induces unregulated growth processes in cells or tissues of multicellular animals, leading to cancer. 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 refers to processes that result in genetic change, and carcinogenesis (the processes of tumor development) may result from mutagenic events. See Mutation, Radiation biology
A mutation is any change in a cell or in an organism that is transmitted to subsequent generations. Mutations can occur spontaneously or be induced by chemical or physical agents. The cause of mutations is usually some form of damage to DNA or chromosomes that results in some change that can be seen or measured. However, damage can occur in a segment of DNA that is a noncoding region and thus will not result in a mutation. Mutations may or may not be harmful, depending upon which function is affected. They may occur in either somatic or germ cells. Mutations that occur in germ cells may be transmitted to subsequent generations, whereas mutations in somatic cells are generally of consequence only to the affected individual.
Not all heritable changes result from damage to DNA. For example, in growth and differentiation of normal cells, major changes in gene expression occur and are transmitted to progeny cells through changes in the signals that control genes that are transcribed into ribonucleic acid (RNA). It is possible that chemicals and radiation alter these processes as well. When such an effect is seen in newborns, it is called teratogenic and results in birth defects that are not transmitted to the next generation. However, if the change is transmissible to progeny, it is a mutation, even though it might have arisen from an effect on the way in which the gene is expressed. Thus, chemicals can have somatic effects involving genes regulating cell growth that could lead to the development of cancer, without damaging DNA.
Cancer arises because of the loss of growth control by dearrangement of regulatory signals. Included in the phenotypic consequences of mutations are alterations in gene regulation brought about by changes either in the regulatory region or in proteins involved with coordinated cellular functions. Altered proteins may exhibit novel interactions with target substrates and thereby lose the ability to provide a regulatory function for the cell or impose altered functions on associated molecules. Through such a complex series of molecular interactions, changes occur in the growth properties of normal cells leading to cancer cells that are not responsive to normal regulatory controls and can eventually give rise to a visible neoplasm or tumor. While mutagens can give rise to neoplasms by a process similar to that described above, not all mutagens induce cancer and not all mutational events result in tumors.
The identification of certain specific types of genes, termed oncogenes, that appear to be causally involved in the neoplastic process has helped to focus mechanistic studies on carcinogenesis. Oncogenes can be classified into a few functionally different groups, and specific mutations in some of the genes have been identified and are believed to be critical in tumorigenesis. Tumor suppressor genes or antioncogenes provide a normal regulatory function; by mutation or other events, the loss of the function of these genes may release cells from normal growth-control processes, allowing them to begin the neoplastic process.
There are a number of methods and systems for identifying chemical mutagens. Mutations can be detected at a variety of genetic loci in very diverse organisms, including bacteria, insects, cultured mammalian cells, rodents, and humans. Spontaneous and induced mutations occur very infrequently, the estimated rate being less than 1 in 10,000 per gene per cell generation. This low mutation rate is probably the result of a combination of factors that include the relative inaccessibility of DNA to damaging agents and the ability of cellular processes to repair damage to DNA.
Factors that contribute to the difficulty in recognizing substances that may be carcinogenic to humans include the prevalence of cancer, the diversity of types of cancer, the generally late-life onset of most cancers, and the multifactorial nature of the disease process. Approximately 50 substances have been identified as causes of cancer in humans, but they probably account for only a small portion of the disease incidence. See Cancer (medicine), Human genetics, Mutation, Radiation biology