Inhibition of chemical carcinogenesis in vivo by azatyrosine.

A single painting of 7,12-dimethylbenza]anthracene on the skin of transgenic mice harboring the human protooncogene c-Ha-ras induced papillomas at 100% incidence after 20 weeks (M. Izawa et al., unpublished data). Application of L-beta-(5-hydroxy-2-pyridyl)alanine (azatyrosine) to the skin at a dose of 2 mg/mouse once every 3 days after initiation with 7,12-dimethylbenza]anthracene greatly reduced the percentage incidence, number per mouse, and size of papillomas. Injection of methylnitrosourea i.p. into transgenic mice induced papillomas in the forestomach after 12 weeks (2 to 12 papillomas/mouse) at 100% incidence (K. Ando et al., Cancer Res., 52: 978-982, 1992). Administration of azatyrosine i.p. at a dose of 2 mg/mouse once every 2 days for 12 weeks after initiation with methylnitrosourea completely prevented the formation of forestomach papillomas. These results clearly indicated that azatyrosine inhibits chemical carcinogenesis in vivo.