N-(4-hydroxyphenyl)retinamide prevents development of T-lymphomas in AKR/J mice

N-(4-Hydroxyphenyl)retinamide (4-HPR), a synthetic retinoic acid derivative, has chemopreventive effects on several types of cancer. We recently showed that 4-HPR is a potent inducer of apoptosis in malignant, but not normal, T-lymphoid cells in vitro. To test 4-HPR's effect in vivo, we used the virus-induced T-lymphoma in AKR/J mice as a model system. The AKR/J mice were fed 4-HPR at 0, 1 or 2 mmole/kg diet, and the animals were monitored as to tumor development, plasma level of 4-HPR, body weight, appetite, and general health. Our results show that in a 19-week period, 4-HPR prevented T-lymphoma development by 40% and 50% of animals fed 1 and 2 mmole 4-HPR/ kg diet, respectively. In the plasma, 4-HPR reached micromolar levels without causing any observable deleterious side-effects. Thus, 4-HPR is potentially useful in chemoprevention of lymphoid cancers.