Rizvi T A, Mathur M, Nayak N C
Department of Pathology, All India Institute of Medical Sciences, New Delhi.
J Natl Cancer Inst. 1987 Oct;79(4):817-30.
Malnourished and well-fed neonatal Holtzman rats 10 days of age were exposed to 3 doses of aflatoxin B1 [(AFB1) CAS: 1162-65-8] at intervals of 96 hours to study the combined effect of malnutrition and cell replication in AFB1-induced hepato-carcinogenesis. The neonatal model made use of the fact that cell replication persists in the liver for 3 weeks of postnatal life. Malnutrition during suckling was induced by adopting the techniques of Widdowson and McCance of increasing the litter size to 16. Following AFB1 administration, the malnourished animals were rehabilitated on a high-protein pellet diet given ad libitum. Preneoplastic lesions and neoplastic nodules were identified in the livers of the 2 groups. Alpha fetoprotein (AFP) was detected in the sera by immunoprecipitation. The preneoplastic lesions appeared earlier, and their progression was faster in the malnourished group as compared to the well-fed animals. By 65 weeks following AFB1 exposure, 6 of 17 (35%) animals from the malnourished group showed neoplastic nodules, whereas no such nodules were observed in the animals from the well-fed group. Neoplastic nodules showed a variable pattern of enzyme activities. Under the electron microscope the changes were again more marked in the animals of the malnourished group as compared to those of the well-fed group. In the former group serum AFP was detected as early as 46 weeks, and by 55-65 weeks almost 50% of the animals from the same group showed positivity for serum AFP. None of the animals from the well-fed group showed any positivity for serum AFP throughout the study. This study thus indicates that preneoplastic lesions-neoplastic nodules are enhanced when cell replication and malnutrition coexist during AFB1-induced hepatocarcinogenesis.
将10日龄营养不良和营养良好的新生霍尔兹曼大鼠每隔96小时暴露于3剂黄曲霉毒素B1 [（AFB1）CAS：1162-65-8]，以研究营养不良和细胞复制在AFB1诱导的肝癌发生中的联合作用。新生模型利用了出生后3周肝脏中细胞复制持续存在这一事实。通过采用威多森和麦坎斯增加窝仔数至16只的技术诱导哺乳期间的营养不良。给予AFB1后，对营养不良的动物随意给予高蛋白颗粒饲料进行康复治疗。在两组动物的肝脏中均发现了癌前病变和肿瘤结节。通过免疫沉淀法在血清中检测甲胎蛋白（AFP）。与营养良好的动物相比，营养不良组的癌前病变出现更早，进展更快。在暴露于AFB1后65周，营养不良组17只动物中有6只（35%）出现肿瘤结节，而营养良好组动物未观察到此类结节。肿瘤结节显示出酶活性的可变模式。在电子显微镜下，与营养良好组相比，营养不良组动物的变化再次更为明显。在营养不良组中，早在46周时就检测到血清AFP，到55 - 65周时，同一组中几乎50%的动物血清AFP呈阳性。在整个研究过程中，营养良好组的动物血清AFP均未显示任何阳性。因此，本研究表明，在AFB1诱导的肝癌发生过程中，当细胞复制和营养不良同时存在时，癌前病变 - 肿瘤结节会增加。
