Antimutagenicity of benzo[a]phenothiazines in chemically induced mutagenesis.

Antipsychotic phenothiazines are known to have antimutagenic activities. The antimutagenicity of seven Benzo[a]phenothiazines was screened against Salmonella typhimurium strain TA98 treated with 4-nitro-o-phenylenediamine (4-NPD) which is a specific mutagen to this strain, and was compared to the antimutagenic activity of chlorpromazine, a 2-chlorphenothiazine derivative which has been shown to be the most effective mutagen inhibitor in the model. Benzo[a]phenothiazines are variously substituted by methyl-, oxo- and/or hydroxyl-substituent(s) at 5, 6, 9 and/or 10 positions(s). 9-Methyl-12H-benzo[a]phenothiazine [3] reduced the 4-NPD induced mutation by 30 percent, being a more potent antimutagenic agent than chlorpromazine. The study of antimutagenicity is of great interest in the development of cancer chemopreventive agents which halt cancer progression in multistage carcinogenesis, where successive mutation sequences are required to evolve into full-fledged metastatic cancer.