Hammond W G, Benfield J R
Department of Surgery, School of Medicine, University of California Davis, Sacramento 95817.
J Cell Biochem Suppl. 1993;17F:104-17. doi: 10.1002/jcb.240531015.
For several widely appreciated reasons, the Syrian hamster has been the most frequently used experimental animal in investigations of conducting airway carcinogenesis. To develop a model where bronchogenic cancer arises focally at a predetermined site, we used the Laskin-Kuschner self-retaining intrabronchial pellet principle, employing a carcinogen-containing silastic polymer sustained release implant (SRI). The SRI is placed in the right lower lobe bronchus via tracheostomy; when modified, the SRI can be removed without loss of the animal. Special preparation of the SRI implant site after fixation but prior to paraffin embedding allows for full histopathological examination of the carcinogen-affected target tissue. Logistic regression analysis of histological findings provides valid quantitative inter-regimen comparisons of histomorphic classifications suitable for determining modulation of carcinogenesis by external influences. Using this model, we demonstrated that the sequential progression of carcinogenesis (SPC) in hamster bronchus is similar to that which occurs in humans and in dogs, including both the ploidy increases that are progressive during the SPC, and the histological patterns of the induced cancers. We have shown genetic variation in susceptibility to carcinogenesis among inbred hamster strains, and have assessed effects of Bacillus Calmette-Guerin (BCG) immunostimulation on the SPC. Time/dose response studies were performed, as were comparisons between four polycyclic aromatic hydrocarbon carcinogens. Systemic administration of 5-azacytidine (AZC) soon after SRI placement was found to inhibit the SPC, to alter the ploidy changes during the SPC and in the eventual cancers, and to affect the degree of differentiation of the cancers. Studies using removable SRIs have assessed the duration of carcinogen exposure required to induce a neoplastic transformation that proceeds to cancer without further carcinogen exposure. Serial syngeneic transplantation of cancers arising in inbred animals has shown that the degree of tumor differentiation is affected by the extent of host immunocompetence, and has also led to development of models for study of the processes of metastasis.
由于一些广为人知的原因，叙利亚仓鼠一直是传导气道致癌作用研究中最常用的实验动物。为了建立一个支气管源性癌在预定部位局灶性发生的模型，我们采用了拉斯金-库施纳支气管内自固定小球原理，使用含致癌物的硅橡胶聚合物缓释植入物（SRI）。通过气管造口术将SRI置于右下叶支气管；经过改进后，可以在不损失动物的情况下取出SRI。在固定后但石蜡包埋前对SRI植入部位进行特殊处理，以便对受致癌物影响的靶组织进行全面的组织病理学检查。对组织学结果进行逻辑回归分析，可为适合确定外部影响对致癌作用调节的组织形态学分类提供有效的定量方案间比较。使用该模型，我们证明了仓鼠支气管中致癌作用的序贯进展（SPC）与人类和犬类中发生的情况相似，包括SPC过程中逐渐增加的倍性以及诱导癌症的组织学模式。我们已经证明近交系仓鼠品系对致癌作用的易感性存在遗传差异，并评估了卡介苗（BCG）免疫刺激对SPC的影响。进行了时间/剂量反应研究，以及四种多环芳烃致癌物之间的比较。发现在放置SRI后不久全身给予5-氮杂胞苷（AZC）可抑制SPC，改变SPC过程中以及最终癌症中的倍性变化，并影响癌症的分化程度。使用可移除SRI的研究评估了诱导肿瘤转化并在无进一步致癌物暴露的情况下发展为癌症所需的致癌物暴露持续时间。近交动物中发生的癌症的系列同基因移植表明，肿瘤分化程度受宿主免疫能力程度的影响，并且还导致了用于研究转移过程的模型的开发。
