a-syngeneic-orthotopic-osteosarcoma-sprague-dawley-rat-model-with

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate

The most recent advance in the treatment of osteosarcoma (OS) occurred in the 1980s when multi-agent chemotherapy was shown to improve overall survival ...

The Johns Hopkins School of Medicine

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.

Polina Sysa-Shah

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