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Peer-reviewedCC BYEnvironmental and molecular mutagenesis

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

  1. 1Department of Cellular and Molecular Biology, Institute of Biosciences, UNESP-São Paulo State University, Botucatu, SP, Brazil.
  2. 2Department of Internal Medicine, Nucleus of Medicine and Experimental Surgery, FCM, UNICAMP-State University of Campinas, Campinas, SP, Brazil.

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.

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BibTeX
@article{ferreira2026gestational,
  title = {{Gestational Low Protein Diet Increases the Susceptibility to N-Bis(2-Hydroxypropyl)nitrosamine-Induced Lung Tumors in Female Wistar Rats.}},
  author = {Vanessa de Cássia Martins Pires Ferreira and Victor Hugo Carvalho and Patrícia Aline Boer and Luís Fernando Barbisan},
  journal = {Environmental and molecular mutagenesis},
  year = {2026},
  month = oct,
  doi = {10.1002/em.70086},
  url = {https://europepmc.org/article/MED/42920348},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Gestational Low Protein Diet Increases the Susceptibility to N-Bis(2-Hydroxypropyl)nitrosamine-Induced Lung Tumors in Female Wistar Rats.
AU  - Vanessa de Cássia Martins Pires Ferreira
AU  - Victor Hugo Carvalho
AU  - Patrícia Aline Boer
AU  - Luís Fernando Barbisan
PY  - 2026
DA  - 2026/10/01
JO  - Environmental and molecular mutagenesis
DO  - 10.1002/em.70086
UR  - https://europepmc.org/article/MED/42920348
AB  - 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.
SN  - 0893-6692
SN  - 1098-2280
ER  -