Roebuck B D, Baumgartner K J, Longnecker D S
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03756.
Carcinogenesis. 1987 Dec;8(12):1831-5. doi: 10.1093/carcin/8.12.1831.
Studies were undertaken to characterize the growth of the azaserine-induced putative preneoplastic lesions in rats and to determine if a single dose of azaserine would be carcinogenic. Male Lewis rats were given a single i.p. injection of 30 mg L-azaserine/kg body weight at 7 weeks of age. A purified diet was fed throughout the study. Rats (10-12 per group) were autopsied at 6, 9, 12, 15 and 18 months post-initiation, and pancreases were quantitatively evaluated to characterize the growth of acidophilic and basophilic foci and nodules (henceforth called foci), and the incidence of neoplasms. All azaserine-treated rats had foci, and at all times approximately equal numbers of acidophilic and basophilic foci were present in the pancreas. The number of basophilic foci increased with time, and while their size also increased, the change was small compared with the increase in size of the acidophilic foci. Conversely, all acidophilic foci appeared to be present by 6-9 months, and their size greatly increased with time. The data suggest that virtually all foci persist rather than regress or remodel. At 9 months the incidence of carcinoma in situ was 30% and by 18 months there was a 100% incidence of pancreatic cancers (58% carcinoma in situ and 42% carcinoma).
开展了多项研究，以表征大鼠中氮杂丝氨酸诱导的假定癌前病变的生长情况，并确定单剂量氮杂丝氨酸是否具有致癌性。7周龄雄性Lewis大鼠经腹腔注射30mg L-氮杂丝氨酸/千克体重。在整个研究过程中喂食纯化饮食。在启动后6、9、12、15和18个月对大鼠（每组10-12只）进行解剖，并对胰腺进行定量评估，以表征嗜酸性和嗜碱性病灶及结节（以下简称病灶）的生长情况以及肿瘤的发生率。所有接受氮杂丝氨酸处理的大鼠均有病灶，且在所有时间点胰腺中嗜酸性和嗜碱性病灶数量大致相等。嗜碱性病灶数量随时间增加，虽然其大小也增加，但与嗜酸性病灶大小的增加相比变化较小。相反，所有嗜酸性病灶在6-9个月时似乎都已出现，且其大小随时间大幅增加。数据表明，几乎所有病灶都持续存在，而非消退或重塑。9个月时原位癌发生率为30%，到18个月时胰腺癌发生率为100%（58%为原位癌，42%为癌）。
