N-methyl N-nitroso Urea induced altered DNA structure initiate hepatocarcinogenesis

The status of inflammatory cytokines IL-1β, IL-6, the anti-apoptotic gene Bcl2 and key transcription factor NFκB in hepatic milieu of N-methyl N-nitroso Urea (MNU) primed Balb/c mice was assessed using RT-PCR and Western blot. Haematoxyline & Eosin (H&E) based histology was performed to evaluate the morphological changes in the cancerous liver cells in respect to control. Laser spectroscopy was used to study the alteration in DNA structure. 40 week MNU treatment induced increased expressions of inflammatory cytokines (IL-1β, IL-6) of Bcl-2 at mRNA level and NFκB and IL-1β at protein level. Alteration in hepatocytes was clearly demonstrated in H&E stained liver sections compared to control. MNU primed liver DNA samples revealed an interference of MNU in nucleic acid bases and structure, reflected by a peak shift at 1456 cm− 1 and shoulder formation at 1357 cm− 1 compared to control DNA samples. This study emphasizes that MNU, a harmful industrial and environmental pollutant, potentially activates inflammatory cytokines (IL-1β, IL-6) in hepatic cells with increased expression of NFκB which might be responsible for hepatocarcinogenesis in Balb/c mice. The outcome sets the basis for further studies on the mitigating effects of dietary biofactors on MNU.

► MNU activates inflammatory cytokines in hepatic cells with increased expression of NFκB.
► Molecular and Biophysical analyses confirm the carcinogenic potential of MNU.
► This is the first report of vivo DNA and MNU intercalations important in mutagenesis.