Gestational Low Protein Diet Increases the Susceptibility to N ‐Bis(2‐Hydroxypropyl)nitrosamine‐Induced Lung Tumors in Female Wistar Rats

ABSTRACT

This study evaluated the susceptibility to lung and kidney carcinogenesis induced by N ‐bis(2‐hydroxypropyl)nitrosamine (DHPN) in female rats whose dams received a low‐protein diet (LPD) during gestation. Pregnant Wistar rats were fed normal protein diet (NPD, 17% protein) or LPD (6% protein). After parturition, all dams were fed NPD until weaning. Then, female offspring were distributed into four groups (NPD, LPD, NPD + DHPN, and LPD + DHPN) and fed NPD. At 6 weeks old, two groups received 0.2% DHPN in drinking water for 4 weeks, and some females were euthanized 24 h after carcinogen stopping, while others were euthanized at Week 26. First, the lung was removed, fixed, histologically processed, and tissue sections were immunohistochemically stained for γ‐H2AX. Second, the lung and kidneys were removed, fixed, histologically processed, and hematoxylin–eosin stained tissue sections were obtained for histopathological analysis. Female rats whose dams received LPD developed a higher mean number of pulmonary epithelial cells positive for γ‐H2AX ( p  < 0.005) and bronchioloalveolar hyperplasia and adenomas ( p  < 0.001 and p  < 0.001) in the lung compared with their counterparts. LPD did not alter the development of atypical tubule hyperplasia in the kidney. These findings indicated that LPD increased DHPN‐induced lung carcinogenesis in female rats.