How does alkylating agents cause DNA damage?

How does alkylating agents cause DNA damage?

Alkylating agents prevent cell division primarily by cross-linking strands of DNA. Because of continued synthesis of other cell constituents, such as RNA and protein, growth is unbalanced, and the cell dies.

Do alkylating agents interfere with DNA synthesis?

Classic alkylating agents interfere with DNA replication by crosslinking DNA strands, DNA strand breaking, and abnormal pairing of base pairs. They exert their lethal effects on cells throughout the cell cycle but tend to be more effective against rapidly dividing cells.

How do alkylating agents cause mutations?

Mutagenicity is related to the ability of alkylating agents to form crosslinks and/or transfer an alkyl group to form monoadducts in DNA. The most frequent location of adducts in the DNA is at guanines. Expressed mutations involve different base substitutions, including all types of transitions and transversions.

What do alkylating agents do to cells?

Alkylating agents keep the cell from reproducing (making copies of itself) by damaging its DNA. These drugs work in all phases of the cell cycle and are used to treat many different cancers, including cancers of the lung, breast, and ovary as well as leukemia, lymphoma, Hodgkin disease, multiple myeloma, and sarcoma.

Which among the following is an alkylating agent?

Some examples of alkylating agents are nitrogen mustards (chlorambucil and cyclophosphamide), cisplatin, nitrosoureas (carmustine, lomustine, and semustine), alkylsulfonates (busulfan), ethyleneimines (thiotepa), and triazines (dacarbazine).

What drugs damage your DNA?

Table 2.1

Base Target Drug
Adenine N7 Cisplatin
Adenine N1 (Uncommon)
Cytosine N3 Fotemustine
Cytosine N1 (Uncommon)

Which of the following alkylating agent below interferes with DNA replication and transcription by modifying DNA bases?

Alkylsulfonates: Busulfan inhibits DNA replication and RNA transcription by DNA alkylation and DNA breaks.

How do chemical agents cause mutation?

There are several ways in which chemicals can induce point mutations. One of the most common is by forming adducts with a particular base in the DNA. Many chemicals that interact with DNA do so by forming covalent bonds between an electrophilic part of the molecule and a nucleophilic part of DNA.

Are alkylating agents mutagens?

The most commonly used chemical mutagens are alkylating agents such as ethylmethane sulfonate and N-methyl-N-nitrosourea that induce point mutations in DNA.

Which are alkylating agents?

Is it possible for cells to overcome the effects of alkylating agents?

Selected Alkylating Agents Can Overcome Drug Tolerance of G 0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice. Clin Cancer Res.

What happens when alkylating agents are added to DNA?

The alkylating agents transfer alkyl (chemical) groups to DNA. DNA alkylation in the nucleus leads to the death of the cell. Once in the cell, the alkylating agents undergo a structural rearrangement that results in the formation of an unstable intermediate, an ethylene immonium ion.

Are alkylating agents mutagenic?

Alkylating agents are mutagenic and genotoxic. The focus of research has therefore been on their ability to damage DNA, and on the processing and consequences of such damage. However, alkylating agents also form adducts with RNA and protein and this is likely to contribute to the cytotoxicity.

What causes alkylation lesions in DNA and RNA?

Alkylation lesions in DNA and RNA result from endogenous compounds, environmental agents and alkylating drugs. Simple methylating agents, e.g. methylnitrosourea, tobacco-specific nitrosamines and drugs like temozolomide or streptozotocin, form adducts at N- and O-atoms in DNA bases.

What is the mechanism of cytotoxicity of alkylating agents?

Mechanism of Cytotoxicity. Although the alkylating agents react with a number of biologic molecules, including amino acids, thiols, ribonucleic acid (RNA), and DNA, a number of lines of evidence have led to the generally accepted conclusion that the cytotoxic effects of the agents are a result of reactions with DNA.

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