Since
pyrimidinone compounds induce
interferon production in several animal species and have potent antivirus activities, it appeared important to determine whether these compounds could also induce antitumor activities in their recipients.
Pyrimidinone compounds 2-amino-5-bromo-6-methyl-4-pyrimidinone (ABMP), 2-amino-5-brome-6-phenyl-4-pyrimidinone (ABPP), and
2-amino-5-iodo-6-phenyl-4-pyrimidinone (
AIPP) were studied for their activities against artificial lung
metastases of the weakly immunogenic spontaneous
fibrosarcoma NFSa, the moderately immunogenic spontaneous mammary
carcinoma MCa-K, and the strongly immunogenic 3-methylcholanthrene-induced
fibrosarcoma FSa syngeneic to inbred C3Hf/Kam mice. In addition, the therapeutic efficacy of ABPP and
AIPP was also determined against spontaneous lung
metastases of NFSa. ABPP and
AIPP given ip at 250 mg/kg for 2 or 3 consecutive days before or after iv inoculatin of NFSa, FSa, or MCa-K cells greatly reduced the number of
tumor nodules developed in the lungs. ABMP, however, was considerably less effective. ABPP and
AIPP were also effective in
therapy of spontaneous lung
metastases of NFSa, especially when these compounds were given before surgical removal of the primary
tumor. Neither ABPP nor
AIPP was effective against
tumor nodules growing in whole-body irradiated (WBI) mice, but both protected mice against enhancement of lung
metastasis formation induced by exposure to whole-body irradiation. ABPP was more effective than
AIPP in inducing production of
interferon in normal mice. When treated with ABPP, WBI mice, however, were unable to produce
interferon. These results show that 6-phenyl-pyrimidinone compounds induce strong antitumor activities in mice, which correlated with neither
tumor immunogenicity nor the ability of these agents to induce
interferon, but which depended on the immune status of the
tumor host.