phosphoramide mustard

Phosphoramide mustard is a toxic metabolite of cyclophosphamide with anticancer activity and ovarian toxicity that induces DNA damage.

Phosphoramide mustard cyclohexanamine is the major metabolite for Cyclophosphamide , with anticancer activitiy. Phosphoramide mustard cyclohexanamine induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response[1][2]. Phosphoramide mustard cyclohexanamine causes cytotoxicity through forming cross-linked DNA adducts which inhibit DNA strand separation during replication[1].Phosphoramide mustard cyclohexanamine destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 48 hours) reduces cell viability in rat spontaneously immortalized granulosa cells (SIGCs)[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 24-48 hours) induces DNA adduct formation[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 24-48 hours) induces ovarian DNA damage in rat ovaries[1].Phosphoramide mustard cyclohexanamine increases DNA damage responses (DDR) gene (Atm, Parp1, Prkdc, Xrcc6, Brca1, Rad51) mRNA expression level[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 24-48 hours) increased DDR proteins[1]. Cell Viability Assay[1] Cell Line: SIGCs Phosphoramide mustard cyclohexanamine (2.1-20.7 mg kg; i.p.; daily; for 5 days) inhibits subcutaneous tumor growth in rats[2].Phosphoramide mustard cyclohexanamine (86.0 mg kg; i.v.) has a plasma disappearance half-life of 15.1 minutes[2]. Animal Model: Rat, subcutaneously implanted Walker 256 carcinosarcoma tumor[2] [1]. Shanthi Ganesan, et al. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells. Toxicol Appl Pharmacol. 2015 Feb 1; 282(3): 252-258. [2]. S Genka, et al. Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat. Cancer Chemother Pharmacol. 1990;27(1):1-7.