Gene amplification and expression of the DNA repair enzyme, N-methylpurine-DNA glycosylase (MPG) in HPV-infected cervical neoplasias

Background: Lethal and mutagenic damages of DNA is caused by a variety of a gents including viruses. It is known that HPV is one of the major causes of cervical carcinogenesis and that cells eliminate DNA lesions with DNA repa ir enzymes. However, the role of N-methylpurine-DNA glycosylase (MPG) is no t known in the development of cervical cancer. Materials and Methods: Multi plex polymerase chain reaction (PCR) was used for the detection and typing of HPV in the biopsy. Gene amplification of MPG was measured by a PCR-based assay. The mRNA levels of MPG were determined by reverse transcription-PCR using hypoxanthine-guanine phosphoribosyl transferase as the reference gen e. An immunohistochemical technique was used to examine the distribution of MPG in the tissues. Results: Of 68 Korean cervical neoplasia patients, 86. 8% showed HPV infection. High-risk HPV 16/18 were the most prevalent but po sitive only in 47.3% of the invasive cancer patients. Gene amplification of MPG was significantly increased in high-risk HPV-infected tissues as compa red to low-risk HPV-infected and normal tissues (p < 0.05). The mRNA levels of MPG were higher in HPV-infected invasive carcinoma than normal cervical tissues. Immunohistochemical staining revealed that the intracellular expr ession and distribution (localization) of MPG altered in the cervical neopl asia. Interestingly, MPG expression in CIN III and invasive carcinoma (IC) was much higher than normal and CIN L Granular positivity of MPG was notabl e in the perinuclear regions of the cytoplasm in HPV-infected invasive canc er. Conclusion: This is the first report on MPG expression in cervical neop lasia. Our results indicate that the gene amplification and expression of M PG were increased in high-risk HPV-infected cervical neoplasias and the int racellular distribution of MPG protein was altered, suggesting a role of MP G in carcinogenesis.