Among the nitro-naphthofurans, 7-methoxy-2-nitro-naphtho[2,1-b]
furan (
R 7000) has been proved to be a very potent
mutagen. The purpose of this study was to demonstrate the carcinogenicity of a
R 7000 to male Wistar rats initially 6 weeks old.
R 7000 was dissolved in
olive oil at a concentration of 1 mg/ml for injection. A S.C. injection of 0.5 ml containing 0.5 mg of
R 7000 was given once a week in the neck of each animal tested. Ten control animals were not injected and 10 animals received a 0.5 ml injection of
olive oil every week to serve as control. The remaining 70 animals were divided into five groups. Four groups of 10 animals received a total of either 2.5 mg, 5 mg, 7.5 mg or 10 mg of
R 7000; the fifth group of 30 animals received 12.5 mg of
R 7000. In animals which did not receive
R 7000, no malignant
tumor was observed. In those to whom
R 7000 was administered
tumors began to appear at the site of the injection after the third month. At the sixth month of the experiment, most of the animals injected had a
tumor at the injection site. The number of
tumor-bearing animals and the time between the first injection and the
tumor appearance were closely related to the dose of
R 7000 injected. These
tumors were high grade
fibrosarcomas, one animal developed a salivary
fibrosarcoma. No other
tumors or
metastases were found in the autopsied animals. The high carcinogenicity of
R 7000 in vivo is analogous to that of
methylcholanthrene. The exact mechanism of action of 2-nitro-naphthofurans as
carcinogens remains to be explained.