Cooperation of MTH1 and MYH proteins in response to oxidative stress induced by chronic γ-radiation

• Mutation in the MYH gene has been suggested as a risk factor for colorectal cancer. MYH plays an important role in mutation avoidance induced by 8-oxo-G:A mispairs which may occur during oxidative stress. Oxidative stress has been suggested to be involved in several human disorders. In the present study we have exposed human lymphoblastoid TK6 cells to very low dose rates of γ-radiation to induce chronic oxidative stress. The aim of the study is to investigate the protective role of MYH and MTH1 against mutagenicity and cytotoxicity induced by chronic radiation in the cells with knockdown MYH or knockdown MYH/MTH1. The levels of MYH and/or MTH1 were knockdown permanently in cells using shRNA. Wild type and knockdown cells were exposed to chronic γ-radiation with the dose rates ranged from 1.4 to 30 mGy/h during growth. The cells were also subjected to an acute high dose rate. Growth rate, clonogenic survival and mutant frequency were analyzed in all cell types. A reduced level of cell growth and survival as well as an increased mutant frequency were observed in cells lacking both MYH and MTH1 proteins as compared to cells lacking only MYH and wild type cells. In conclusion, our results suggest that MYH and MTH1 cooperatively respond to oxidative stress induced by chronic radiation in human cells.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

MYH

MTH1

oxidative stress

mutation rate

low dose rate radiation

ionizing radiation

molekylärgenetik

Molecular Genetics

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)