Oncolytic adenoviruses replicate selectively within and lyse malignant cells. As such, they are being developed as anticancer therapeutics. However, the sensitivity of ovarian cancers to adenovirus cytotoxicity varies greatly, even in cells of similar infectivity. Using both the adenovirus E1A-CR2 deletion mutant dl922-947 and WT adenovirus serotype 5 in a panel of human ovarian cancer cell lin...

ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partia...

Nucleotide excision repair (NER) removes the major UV photolesions from cellular DNA. In humans, compromised NER activity is the cause of several photosensitive diseases, one of which is the skin-cancer predisposition disorder, xeroderma pigmentosum (XP). Two assays commonly used in measurement of NER activity are 'Unscheduled DNA synthesis (UDS)', and 'Recovery of RNA synthesis (RRS)', the lat...

Removal of alkylation products from the DNA of mammalian cells was studied in nondividing human lymphocytes damaged with 7-bromomethylbenz(a)anthracene, a carcinogenic alkylating agent that produces chemically stable products upon reaction with DNA. The reaction of 7-bromomethylbenz(a)anthracene-3 H with cells in lymphocyte culture was complete in about 20 mm. The unlabeled compound induced uns...

Immunosuppressive medication in renal transplant recipients (RTR) strongly increases the risk of cancers on sun-exposed skin. This increased risk was considered an inevitable collateral effect of immunosuppression, because UV-induced carcinomas in mice were found to be highly antigenic. Here, we posed the question whether immunosuppression also increases the frequency of p53-mutant foci ('p53 p...

The hepatitis B virus X protein (HBx) is a broadly acting transactivator implicated in the development of liver cancer. Recently, HBx has been reported to interact with several different cellular proteins, including our report of its binding to XAP-1, the human homolog of the simian repair protein UVDDB. In the present study, several HBx mutants were used to localize the minimal domain of HBx r...

Compounds of lead and cadmium have been shown to be carcinogenic to humans and experimental animals. However, the underlying mechanisms are still not understood. In mammalian cells in culture, lead(II) is weakly mutagenic after long incubation times and generates DNA strand breaks only after treatment with high, toxic doses. Cadmium(II) induces DNA strand breaks and chromosomal aberrations, but...

Fifty xeroderma pigmentosum patients in Japan were examined for clinical characteristics and DNA repair of their cells, Skin cancers developed in 22 patients. Most of the patients without skin cancers were children, except for 5 older patients who had intermediate or nearly normal levels of DNA repair in their cells. All patients younger than 10 years old had no or very low activity of unschedu...

Down's syndrome (DS) is the most common chromosomal abnormality in human. Subjects with DS are known to be peridisposed to develop leukemia. The molecular basis of the association between DS and leukemia is unknown. The unscheduled DNA synthesis (UDS) test measure the ability of DNA-repair in mammalian cells after excision of a stretch of DNA containing the region of damage induced by chemical ...