Effect of p53 tumor suppressor on nucleotide excision repair in human colon carcinoma cells treated with 4-nitroquinoline 1-oxide

In probing the mechanism of nucleotide excision repair (NER) in response to 4-nitroquinoline 1-oxide (4NQO)-induced DNA damage, the effect of p53 tumo r suppressor was investigated. The effect of p53 protein on the repair of d amaged DNA was examined by comet assay. Expression of p53 and p21(Waf1/Cip1 ) proteins was measured by the Enzyme-linked immunosorbent assay (ELISA) an d immunocytochemistry, respectively. Compared to RKO cells having the wild- type p53 gene, increased cytotoxicity by 4NQO was observed in RKOmp53 cells with a mutation in p53 protein. DNA single strand breaks (SSB), indicative of the DNA repair, were considerably increased in 4NQO-treated RKO cells. Also, the expression of p53 and p21 proteins was significantly increased in 4NQO-treated RKO cells. In RKOmp53 cells, no effect of 4NQO on p21 express ion was observed. Our findings suggest that 4NQO-induced NER is p53-depende nt and involves up-regulation of its downstream regulator, p21(Waf1/Cip1) p roteins.