Svensson S, Heyden G
Int J Oral Surg. 1982 Feb;11(1):52-8. doi: 10.1016/s0300-9785(82)80049-5.
The development of irreversible precancerous changes in the palatal mucosa of the rat was studied macroscopically and histologically after painting the palate 3 times a week with 0.5% 4-nitroquinoline-N-oxide for 1-22 weeks. Control animals were painted with the solvent propylene glycol. After the application periods, the spontaneous development of premalignant epithelial changes and carcinomas was recorded by repeated biopsy procedures. Short application periods (1-6 weeks) were consistently followed by prolonged expectancy periods (51-80 weeks) before the development of carcinomas. Comparably long application periods (more than 12 weeks), however, induced carcinomas after relatively short expectancy periods (8-21 weeks). The total experimental periods (application plus expectancy periods) for animals painted for more than 12 weeks were frequently less than 1/2 of that for animals painted for 1-6 weeks. All experimentally induced tumours represented highly differentiated squamous cell carcinomas with excessive keratin formation. They were consistently preceded by different stages of epithelial dysplasia. Advanced carcinomatous changes were frequently not visible macroscopically. Irreversible precancerous transformation had already occurred in epithelium at early hyperplastic, non-dysplastic stages.
每周用0.5%的4-硝基喹啉-N-氧化物对大鼠腭部进行3次涂抹，持续1 - 22周，之后对大鼠腭部黏膜不可逆癌前病变的发展进行了宏观和组织学研究。对照动物用溶剂丙二醇进行涂抹。在涂抹期结束后，通过重复活检程序记录癌前上皮变化和癌的自然发展情况。短涂抹期（1 - 6周）后，在癌发生之前会持续出现较长的预期期（51 - 80周）。然而，相当长的涂抹期（超过12周）会在相对较短的预期期（8 - 21周）后诱发癌症。涂抹超过12周的动物的总实验期（涂抹期加预期期）常常不到涂抹1 - 6周动物的总实验期的1/2。所有实验诱导的肿瘤均为高分化鳞状细胞癌，伴有过度角化形成。它们之前总是伴有上皮发育异常的不同阶段。晚期癌性变化在宏观上常常不可见。在早期增生、无发育异常阶段，上皮中就已经发生了不可逆的癌前转变。
