Natural evolvement of lung tumors induced by N-ethyl-N-nitrosourea (ENU) and the impact of a high sucrose-high fat diet on tumor evolvement assessed by tumor histology in inbred BALB/c and C57BL/6J mice

Lijun Dai, Yueling Huang, Bingfei Ye, Xinbin Yang, Shengli An, Min Hou


Background: The model of lung tumors transplacentally induced by N-ethyl-N-nitrosourea (ENU) in inbred BALB/c and C57BL/6J mice was used to investigate the impact of a high sucrose-high fat (HSHF) diet on lung tumorigenesis.
Methods: The offspring was separated by gender and randomly divided into 2 subgroups in both ENU- and buffer-treated groups at the time of weaning. One subgroup was put on the standard diet and the other on the HSHF diet from weaning to the age of 24 weeks. The entire lungs went through a standard process of paraffin-embedded blocks. Every lung block was cut in serial sections but one in every five sections was saved to generate step sections that were stained by hematoxylin and eosin. The tumor histology was assessed on the step sections.
Results: At 24-week checkpoint, a spectrum of histological changes was observed in the mice on both diets. Specifically, they presented as alveolar hyperplasia, adenomas and adenomas with nuclear dysplasia at various degrees. Those tumors were actually at different developmental stages. Lung adenocarcinomas were developed in mice on the HSHF diet. A cluster of tumor cells with wide foamy or clear or signet-ring shaped cytoplasm (fatty changes) appeared in a low frequency on the HSHF diet.
Conclusions: The observed histological changes indicated that lung tumors were developed at different times and evolved at different paces. The HSHF diet accelerated the course of tumor evolvement. Tumor cells with fatty changes might be induced by the HSHF diet.