Salmon R J, Buisson J P, Aussepe L, Royer R
Carcinogenesis. 1985 Jan;6(1):109-11. doi: 10.1093/carcin/6.1.109.
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.
在硝基萘并呋喃类化合物中,7-甲氧基-2-硝基萘并[2,1-b]呋喃(R 7000)已被证明是一种极强的诱变剂。本研究的目的是证明R 7000对初始年龄为6周的雄性Wistar大鼠的致癌性。将R 7000溶解于橄榄油中,配制成浓度为1 mg/ml的注射液。每周一次在每只受试动物的颈部皮下注射0.5 ml含0.5 mg R 7000的溶液。10只对照动物不注射,另外10只动物每周注射0.5 ml橄榄油作为对照。其余70只动物分为五组。四组每组10只动物分别接受总量为2.5 mg、5 mg、7.5 mg或10 mg的R 7000;第五组30只动物接受12.5 mg的R 7000。未接受R 7000的动物未观察到恶性肿瘤。在给予R 7000的动物中,第三个月后肿瘤开始出现在注射部位。实验第六个月时,大多数注射的动物在注射部位出现肿瘤。荷瘤动物的数量以及首次注射与肿瘤出现之间的时间与注射的R 7000剂量密切相关。这些肿瘤为高级别纤维肉瘤,1只动物发生了涎腺纤维肉瘤。在尸检动物中未发现其他肿瘤或转移灶。R 7000在体内的高致癌性与甲基胆蒽类似。2-硝基萘并呋喃作为致癌物的确切作用机制仍有待阐明。