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alkylating agents

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alkylating agents [al´kĭ-lāt-ing]
a group of synthetic compounds containing alkyl groups that combine readily with other molecules. Their action seems to be chiefly on the DNA in the nucleus of the cell, so that they are cell cycle phase nonspecific. They cross-link the strands of DNA, preventing its replication and the transcription of RNA; the major site of action is on the base guanine. They are primarily used in chemotherapy of cancer (see antineoplastic therapy). However, they do not damage malignant cells selectively, but also have a toxic action on normal cells; all killing occurs primarily in rapidly proliferating tissue. Locally they cause blistering of the skin and damage to the eyes and respiratory tract. Systemic toxic effects are nausea and vomiting, reduction in both leukocytes and erythrocytes, hemorrhagic tendencies, amenorrhea or impaired spermatogenesis, damage to the intestinal mucosa, and alopecia. Among the agents of this group used in therapy are busulfan, cyclophosphamide, ifosfamide, and thiotepa; the nitrogen mustardschlorambucil, melphalan, and mechlorethamine; and the nitrosoureascarmustine, lomustine, and streptozocin. They may be carcinogenic in humans; some have been linked to bladder cancer and acute leukemia. However, the major benefits obtained in treating diseases such as lymphoma, Hodgkin's disease, breast cancer, and multiple myeloma far outweigh the risks of developing a second malignancy.

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VAL-083 is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and lung cancer Based on published research, the mechanism of action of VAL-083 is understood to be a bi-functional alkylating agent; however, the functional groups associated with alkylating events has been shown to differ from other alkylating agents used in the treatment of GBM.
Our study showed that these alkylating agents are present at levels sufficient to cause DNA damage and could potentially have adverse implications to human health, particularly in the case of the development of oral cancer for BQ chewers," they said.
Osteoporosis is one such potential complication that can result from treatment with alkylating agents and the steroids that are often given with chemotherapy.

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