Kanno J, Maronpot R R, Takahashi M, Kasuga T, Hayashi Y
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Carcinogenesis. 1993 Nov;14(11):2389-96. doi: 10.1093/carcin/14.11.2389.
Six-week-old male F344 rats were divided into 4 groups. Rats in Groups 1 (n = 16) and 3 (n = 14) received a s.c. injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN) (2800 mg/kg) in experimental week 1 while rats in Groups 2 (n = 5) and 4 (n = 5) received saline. From weeks 2-20, all rats were given an iodine deficient (I-def) diet and tap water. Groups 1 and 2 were killed for the measurements of thyroid-stimulating hormone (TSH), thyroxine (T4), the maximum thyroid width (MTW), thyroid weight, morphology, morphometrics and proliferating cell nuclear antigen (PCNA) labeling index (LI). The thyroids of the rats in Group 3 and 4 were surgically exposed and the MTWs were measured. These latter rats were given basal diet for 6 weeks to recover from iodine deficiency, and then killed for the same measurements. Thyroid nodular lesions in Group 1 rats were classified into five categories (NL0, NL1, NL2, NL3 and NL4) based upon incremental cellular and structural atypia. Two types of regressive nodules (NL'0 and NL'1+2) were identified in the recovered rats as the regressed form of NL0, NL1 and NL2 lesions. NL3 and NL4 nodules were seen in Groups 1 and 3. The mean number of combined NL0, NL1 or NL2 lesions was 28.44 +/- 6.12 nodules per rat (NPR) in Group 1 rats and the mean number of NL'0 and NL'1+2 lesions was 28.07 +/- 13.05 NPR in Group 3 rats. The mean number of NL3 or NL4 lesions was 1.70 NPR in Group 1 rats and 3.42 NPR in Group 3 rats. The LIs were NL0 (6.4 +/- 2.5%), NL1 (7.7 +/- 4.4%), NL2 (0.7 +/- 0.3%), NL3 (7.5 +/- 1.3%) and NL4 (14.4 +/- 5.3%) in Group 1 rats and NL'0 (< 0.001%), NL'1 + 2 (< 0.01%), NL3 (9.0 +/- 4.4%) and NL4 (23.3 +/- 17.8%) in Group 3 rats. The thyroid weights of Group 4 rats were 41% of Group 2 rats. The volume fraction (VF) of the non-NL3, non-NL4 areas in Group 3 rats was 40% of that in Group 1 rats. However, the VF of NL3 or NL4 lesions in Group 3 rats was 520% of that of Group 1 rats. In summary, the growth of the NL0, NL1 and NL2 lesions was TSH-dependent, whereas NL3 and NL4 lesions were TSH-independent.(ABSTRACT TRUNCATED AT 400 WORDS)
六周龄雄性F344大鼠被分为4组。第1组（n = 16）和第3组（n = 14）的大鼠在实验第1周接受皮下注射N-双（2-羟丙基）亚硝胺（DHPN）（2800 mg/kg），而第2组（n = 5）和第4组（n = 5）的大鼠接受生理盐水注射。从第2周到第20周，所有大鼠均给予缺碘（I-def）饮食和自来水。第1组和第2组大鼠被处死，用于测量促甲状腺激素（TSH）、甲状腺素（T4）、最大甲状腺宽度（MTW）、甲状腺重量、形态、形态计量学以及增殖细胞核抗原（PCNA）标记指数（LI）。第3组和第4组大鼠的甲状腺通过手术暴露并测量MTW。后一组大鼠给予基础饮食6周以从碘缺乏中恢复，然后处死进行相同的测量。第1组大鼠的甲状腺结节性病变根据细胞和结构异型性的增加分为五类（NL0、NL1、NL2、NL3和NL4）。在恢复的大鼠中鉴定出两种类型的退行性结节（NL'0和NL'1 + 2），作为NL0、NL1和NL2病变的退行形式。第1组和第3组出现了NL3和NL4结节。第1组大鼠中合并的NL0、NL1或NL2病变的平均数量为每只大鼠（NPR）28.44±6.12个结节，第3组大鼠中NL'0和NL'1 + 2病变的平均数量为28.07±13.05 NPR。第1组大鼠中NL3或NL4病变的平均数量为1.70 NPR，第3组大鼠中为3.42 NPR。第1组大鼠中LI分别为NL0（6.4±2.5%）、NL1（7.7±4.4%）、NL2（0.7±0.3%）、NL3（7.5±1.3%）和NL4（14.4±5.3%），第3组大鼠中NL'0（<0.001%）、NL'1 + 2（<0.01%）、NL3（9.0±4.4%）和NL4（23.3±17.8%）。第4组大鼠的甲状腺重量为第2组大鼠的41%。第3组大鼠中非NL3、非NL4区域的体积分数（VF）为第1组大鼠的40%。然而，第3组大鼠中NL3或NL4病变的VF为第1组大鼠的520%。总之，NL0、NL1和NL2病变的生长依赖于TSH，而NL3和NL4病变则不依赖于TSH。（摘要截断于400字）
