Onset of the lymphocytic infiltration and hyperplasia preceding the proliferation in F1 mouse lungs from the N- ethyl- N-nitrosourea exposed mothers: Prevention during the lactation period by inositol hexaphosphate

Publication date: Available online 2 April 2015 Source:Toxicology Reports Author(s): Satya Sahay , Prakash Tiwari , Krishna P. Gupta Maternal exposure to a carcinogen is associated with increased risk of different cancers in the offspring. The foetus is highly sensitive to carcinogens and this contributes to the foetal basis of the onset of disease. The better understanding of the molecular mechanisms involved in the early stage of lung tumorigenesis in the offspring is needed for the newer preventive strategies. We evaluated the effects of N-ethyl-N-nitrosourea (ENU) given on the 17th day of gestation and antitumor agent inositol hexaphosphate (IP6) to the mothers at the early stage of lung tumorigenesis in F1 mice. There was no treatment related effects on the litter size or body weight of the F1 mice at the PND12 or 24. Analysis of PCNA, NF-κB (p50), IL-6, COX-2, pSTAT3, STAT3, caspase-3, caspase-9, PARP, Akt signalling and downstream cyclinD1 along with miR-155, suggested the modulation of proliferation, inflammation and apoptosis at PND12 and 24. IP6 administration to the predisposed mothers prevented the proliferation, inflammation and enhanced apoptosis in F1 lung as showed by a reduction in PCNA, NF-κB (p50), IL-6, COX-2, pSTAT3, STAT3, miR-155 and increase in caspases, cleavage of poly (ADP-ribose) polymerase. IP6 administration also inhibited the activation of Akt, and cyclinD1. Our study show that tumorigenic changes take place in the lungs of the F1 gener...
Source: Toxicology Reports - Category: Toxicology Source Type: research