Antimutagenicity of benzo[a]phenothiazines in chemically induced mutagenesis.
The antimutagenicity of seven benzo[a]phenothiazines was screened against Salmonella typhimurium strain TA98 treated with 4-nitro-o-phenylenediamine which is a specific mutagen to the strain, and the results were compared to the antimutagenic activity of chlorpromazine (8), one of the 2-chlorophenothiazine derivatives-which have been shown to be the most effective mutagen inhibitors. Benzo[a]phenothiazines with methyl, oxo or hydroxyl substituent(s) at position 5, 6, 9 or 10 were used in the screening tests. 6-Hydroxy-5-oxo-5H-benzo[a]phenothiazine (6) reduced the induced mutation by 27%, being a more potent antimutagenic agent than chlorpromazine (8). The study of antimutagenicity is of great interest for the development of cancer chemopreventive agents which stop cancer progression in multistage carcinogenesis in which successive mutation sequences are required for a progression into full-fledged metastatic cancer.
Tanaka
M
M
Faculty of Medicine, Institute of Microbiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Wayda
K
K
Molnár
J
J
Párkányi
C
C
Aaron
J J
JJ
Motohashi
N
N
D016587:Antimutagenic Agents / Q000494:pharmacology*; D010640:Phenothiazines / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D016587:Antimutagenic Agents; D010640:Phenothiazines