Which of the following is the main mechanism by which the mechlorethamine exes its cell killing?
Alkylating DNA, causing cross-links between parallel DNA strands Vincristine and the other vinca alkaloids bind to tubulin and impair microtubular assembly, preventing mitosis (M-phase-specific). Mechlorethamine, like cyclophosphamide (and carmustine and several others), is an alkylating agent. They are called bifunctional alkylating agents because they can covalently bind to DNA in two places ("nucleophilic attack"), thereby forming cross-links between two adjacent strands or between two bases in one strand. This ultimately disrupts DNA and RNA synthesis or may cause strand breakage. Cyclophosphamide (which can be considered the prototype of the alkylating agents) is actually a pro- drug--it requires metabolic activation in order for its effects to occur. Cyclophosphamide (and other alkylating agents) are cell cycle-nonspecific, although their efficacy is greater when cells are not in G0.Bleomycin, dactinomycin, and doxorubicin are good examples of drugs that intercalate in DNA strands. Thus, the altered DNA no longer serves as an adequately precise template for eventual synthesis of more functional DNA and RNA. They are classified as antitumor antibiotics. Etoposide and topotecan are examples of drugs that inhibit topoisomerase 11. The consequence is inhibited ability of affected cells to repair DNA strand breaks. This stops the cell cycle in G2 - The taxoid (e.g., paclitaxel) impairs mitosis, but by stabilizing assembled microtubules rather than by exeing a vinca alkaloid-like inhibition of microtubular assembly.
Alkylating DNA, causing cross-links between parallel DNA strands
Blocking microtubular assembly and mitosis during M-phase
Inhibiting topoisomerase, preventing repair of DNA strand breaks
Intercalating in DNA strands, there by preventing DNA replication by Mrna