Procarbazine hydrochloride (NSC-77213 HCl) is the hydrochloride salt of a methylhydrazine derivative with antineoplastic and mutagenic activities. Although the exact mode of cytotoxicity has not been elucidated, procarbazine, after metabolic activation, appears to inhibit the trans-methylation of methionine into transfer RNA (t-RNA), thereby preventing protein synthesis and consequently DNA and RNA synthesis. This agent may also undergo auto-oxidation, resulting in the formation of cytotoxic free radicals which damage DNA through an alkylation reaction.

Procarbazine plus Cu(II) induce piperidine-labile and formamidopyrimidine-DNA glycosylase-sensitive lesions at the 5'-ACG-3' sequence, complementary to a hotspot of the p53 gene, and the 5'-TG-3' sequence. Procarbazine causes DNA damage through non-enzymatic formation of the Cu(I)-hydroperoxo complex and methyl radicals. [1] Procarbazine has a strong clastogenic effect in hematopoietic cells and is mutagenic in a variety organs after high dose treatment. [2]

Procarbazine causes significant decrease in testicular and epididymal weight and a drastic reduction in haploid cells and spermatogenic arrest, demonstrating variation among the test golden hamster. [3] Procarbazine produces a dose-dependent potentiation of MAO A in brown adipose tissue, the elevation being more pronounced following monomethylhydrazine, with activity rising to 350% of that in control homogenates in rats. Procarbazine or monomethylhydrazine reduces metabolism of this amine by a similar degree as had been determined ex-vivo in blood vessel homogenates. [4] Procarbazine is mutagenic, clastogenic and teratogenic in a wide range of test systems of varying complexity and a wide-spectrum carcinogen in rodents and monkeys, causing tumours of the haemopoietic system, the mammary gland, the lung and the nervous system. Procarbazine in vivo undergoes a complex series of metabolic changes that result in the generation of a number of chemically reactive species, including methylating agents and free radicals. [5]