The nitrosoureas

The discovery in the 1950s of the anti-cancer properties of N'-nitroso-N-nitrosoguanidine led to synthesis of many chloroethyl nitrosoureas. They tend to form C-G DNA intrastrand cross-links.

Not all group members form cross-links e.g. methylnitrosourea and streptozocin modify DNA by covalent bonding of a methyl group at the O6 position of guanine. BCNU is a small lipophilic molecule and is used to treat CNS tumours and as a conditioning agent in high-dose therapy. Toxicities include:

♦ Myelosuppression.

♦ Veno-occlusive disease.

♦ Pulmonary fibrosis.

CCNU^ is very similar to BCNU^, administered orally, but can also cause nephrotoxicity.

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