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

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.