論文

査読有り 国際誌
2020年4月6日

Prenatal stress enhances NNK-induced lung tumors in A/J mice.

Carcinogenesis
  • Tomoaki Ito
  • Harumi Saeki
  • Xin Guo
  • Polina Sysa-Shah
  • Jonathan Coulter
  • Kellie Tamashiro
  • Richard S Lee
  • Hajime Orita
  • Koichi Sato
  • Shun Ishiyama
  • Alicia Hulbert
  • William E Smith
  • Lisa A Peterson
  • Malcolm V Brock
  • Kathleen L Gabrielson
  • 全て表示

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/carcin/bgaa033

Children born to women who experience stress during pregnancy have an increased risk of cancer in later life, but no previous animal studies have tested such a link. We questioned whether prenatal stress in A/J mice affected the development of lung tumors after postnatal response to tobacco specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Timed-bred A/J mice were randomly assigned on gestation day 12.5 to prenatal stress (PS) by restraint for 5 consecutive days or control (no restraint). Adult offspring of control and stressed pregnancies were all treated with three NNK injections (50 mg/kg every other day) and euthanized 16 weeks later to examine their lungs. Compared to controls, PS dams exhibited significantly increased levels of plasma corticosterone, increased adrenal weights, and decreased fetus weights without fetal loss. Prenatally stressed litters had a significantly higher neonatal death rate within first week of life, and surviving male and female offspring developed lung epithelial proliferations with increase multiplicity, increased area, and aggressive morphology. Prenatal stress also induced more advanced atypical adenomatous hyperplasia (AAH) lesions. We found no difference in lung NNK-derived methyl DNA adducts, but prenatal stress did significantly enhance CD3+ T cell and Foxp3+ T cell tumor infiltration. Prenatal stress significantly increases multiplicity, area of NNK-induced lung tumors and advanced morphology. Prenatal stress did not affect production of NNK-derived methyl DNA adducts but did increase lymphocytic infiltration of lung tumors. To our knowledge, this is the first animal model of prenatal stress with evaluation of cancer development in offspring.

リンク情報
DOI
https://doi.org/10.1093/carcin/bgaa033
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32249286
ID情報
  • DOI : 10.1093/carcin/bgaa033
  • PubMed ID : 32249286

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