McMillan M D, Smith C J, Ramirez V
Department of Oral Biology and Oral Pathology, University of Otago, Dunedin, New Zealand.
Arch Oral Biol. 1994 Jun;39(6):519-28. doi: 10.1016/0003-9969(94)90149-x.
Fifty 4- to 6-week-old male random-bred golden hamsters were injected intraperitoneally with a weight-related dose (12.5 mg/kg body weight) of N-methyl-N-nitrosourea (NMU) three times a week for 4 weeks. Groups of seven animals were killed 10, 16 and 22 weeks after the first injection. The palatal gingiva from six animals and the intermolar mucosa from 21 animals was examined. Seven male age-matched untreated control animals were killed at each period. Although all NMU-treated hamsters showed dysplastic and neoplastic changes similar to those in human oral squamous-cell carcinoma, other changes such as acantholytic dyskeratosis, invading cysts, duct-like structures and basaloid islands and cords were not. The extent and severity of the changes increased with time so that by 22 weeks there was extensive involvement of the palatal bone and marrow spaces, the molar periodontal ligament and the greater palatine neurovascular bundle by neoplastic epithelium. The invading epithelium was derived from the junctional, crevicular and palatal gingival and intermolar epithelium. The latent period for the crevicular and junctional epithelia was shorter than that for the palatal gingival and intermolar epithelium. The invasive changes from the latter epithelium were often preceded by exophytic changes such as epithelial projections, papillae and papillomas. Such changes were infrequent for the gingival, crevicular and junctional epithelia. The study shows that intraperitoneal NMU acts as a complete carcinogen on the palatal gingival and intermolar epithelium in hamsters.
50只4至6周龄的雄性随机繁殖金黄仓鼠,每周腹腔注射与体重相关剂量(12.5毫克/千克体重)的N-甲基-N-亚硝基脲(NMU),共注射4周,每周3次。在首次注射后10、16和22周处死每组7只动物。检查了6只动物的腭龈和21只动物的磨牙间黏膜。在每个时间段处死7只年龄匹配的未处理雄性对照动物。尽管所有接受NMU处理的仓鼠均表现出与人类口腔鳞状细胞癌相似的发育异常和肿瘤性变化,但棘层松解性角化不良、侵袭性囊肿、导管样结构以及基底样岛和索等其他变化则未出现。这些变化的程度和严重程度随时间增加,以至于到22周时,肿瘤上皮广泛累及腭骨和骨髓腔、磨牙牙周韧带以及腭大神经血管束。侵袭性上皮源自结合上皮、龈沟上皮、腭龈上皮和磨牙间上皮。龈沟上皮和结合上皮的潜伏期短于腭龈上皮和磨牙间上皮。后者上皮的侵袭性变化之前常伴有外生性变化,如上皮突起、乳头和乳头状瘤。而牙龈、龈沟和结合上皮的此类变化并不常见。该研究表明,腹腔注射NMU对仓鼠的腭龈上皮和磨牙间上皮起完全致癌物的作用。