Alkylation: Function, Tasks, Role & Diseases

Alkylation characterizes the transfer of an alkyl group from one molecule to another. Alkylations have mutagenic and carcinogenic effects, as DNA and RNA are often attacked and altered by alkylating agents. The so-called alkylating agents are used in medicine, on the one hand, to inhibit cell growth as cytostatics and, on the other hand, are triggers of cancer or cause hereditary damage in the offspring.

What is alkylation?

Alkylation characterizes the transfer of an alkyl group from one molecule to another. Often, DNA and RNA are attacked and altered by alkylating agents. Certain chemical substances develop mutagenic and carcinogenic effects through their ability to induce alkylation. Alkylation involves the transfer of alkyl groups. A special case of alkylations is methylation. The methyl group also belongs to the alkyls. However, methylations always take place under physiological conditions in the body, while alkyl groups with more than one carbon atom are usually induced by substances foreign to the body. Methylations of DNA are responsible for epigenetic changes. In addition, many other methylation reactions also take place in the organism. In these reactions, methyl groups are transferred to specific functional groups such as hydroxy, amino or sulfhydryl groups. When ethyl, propyl or even higher-chain alkyl groups are transferred, the genetic material in particular is affected. The more alkyl groups bind to the DNA, the more frequently the DNA strands break. Furthermore, different strands can also bind to each other. Finally, higher chain alkylations always lead to the alteration of the nucleic acid molecules. As a result of the nucleic acid changes, cell growth is inhibited, among other things.

Function and task

Because of the growth inhibitory effect of alkylations, potential applications in cancer treatment are suggested. Although alkylating compounds have a carcinogenic effect, they can simultaneously stop the uninhibited growth of existing cancer cells. By destroying the DNA, growth is interrupted in proliferating cells (dividing cells) at so-called checkpoints of the cell cycle. The cell slowly dies. This is true for cancer cells as well as for cells that are subject to strong growth under physiological conditions, such as immune cells, mucosal cells, hair root cells and germ cells. While changes in DNA occur in every cell, the effect and intensity is greatest in proliferating cells. The cells that divide particularly rapidly are thus affected the most. This is the basis for the selective effect of cytostatic drugs on cancer cells. For this reason, many alkylating cytostatic agents are used for cancer therapy as part of chemotherapy. With long-term use of these substances, their harmfulness increases, since slower-growing cells are also genetically modified to a lesser extent. In the special case of methylation, DNA is also methylated to a large extent. However, no genetic change takes place. The base sequence remains unchanged. Methyl groups are only attached to cytidine. The methylated areas of the DNA are inactive, so that the genetic code can no longer be read here. This leads to epigenetic changes in the DNA. The DNA is thus modified, but the genetic code remains intact. Due to epigenetic changes, the body also changes in the form of modifications of the phenotype. It is these processes that are responsible for the influence of the environment on the formation and expression of characteristic traits, which are not completely determined by the genotype. The differentiation of individual cells into different organs and tissues also has to do with epigenetic changes. Differentiation is caused by the differential activity of genes in different cell types.

Diseases and disorders

The basis of chemotherapy is based on the cytostatic effect of alkylating substances. At the same time, however, the severe side effects of chemotherapeutic agents are also due to their alkylating effects. These agents exert their therapeutic effect against cancer due to their growth-inhibiting influence on cells. Cancer cells grow the fastest. Therefore, they are affected the most. However, the growth of immune cells, mucosal cells or germ cells is also impaired.As a result, the well-known side effects of chemotherapy occur, which manifest themselves in susceptibility to infection, nausea, vomiting, anemia, hair loss, dry mucous membranes and other unpleasant symptoms. Important cytostatic agents for chemotherapy represent derivatives of nitrogen-lost compounds, alkylsulfonates, nitrosoureas and various other groups of substances. What they all have in common is an alkylating effect on DNA, which is destroyed in the process. All active substances can be used for cancer therapy, but have the corresponding unpleasant side effects. If a healthy person comes into contact with these substances, his risk of developing cancer increases. The short-term effect of these substances is to stop cell divisions and cause the cells to die. The gradual changes in DNA in slow-growing cells can also lead to their transformation into cancer cells in the longer term. Alkylating chemical compounds in industry and the food industry also exert carcinogenic and mutagenic effects in some cases. These include dimethyl sulfate in the chemical industry and the cold sterilizers dimethyl dicarbonate and diethyl dicarbonate in the food industry. The body’s own methylations can also lead to diseases if they occur incorrectly. Thus, increased or decreased gene activity is based on the methylation of DNA. However, when methylation is faulty, diseases develop. For example, tumors can develop as a result of incorrect gene activation. This is true if a regulatory gene for cell division is inactive. But the activation of genes that should normally be inactive can also lead to the degeneration of cells. In various tumors, divergent methylation patterns to the corresponding healthy tissues have been found. It does not matter whether the degree of methylation is too strong or too weak.