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

作者：Verma Shalini; Bahorun Theeshan^*; Kumar Arvind

来源：Preventive Medicine, 2012, 54: S130-S136.

DOI：10.1016/j.ypmed.2012.01.005

• N-methyl N-nitroso Urea (MNU)
• Liver cancer
• Inflammatory cytokines
• Raman spectroscopy
• Balb/c mice

The status of inflammatory cytokines IL-1 beta, IL-6, the anti-apoptotic gene Bcl2 and key transcription factor NF kappa B in hepatic milieu of N-methyl N-nitroso Urea (MNU) primed Balb/c mice was assessed using RT-PCR and Western blot. Haematoxyline %26 Eosin (H%26E) 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-1 beta, IL-6) of Bcl-2 at mRNA level and NF kappa B and IL-1 beta at protein level. Alteration in hepatocytes was clearly demonstrated in H%26E 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-1 beta, IL-6) in hepatic cells with increased expression of NF kappa B 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.

• 出版日期2012-5-1