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Biomedical subjects

R A Moorehead

Publications and source records attributed to R A Moorehead.

4 recordsLinked to original sources
PubMed1996

Nucleotide excision repair in the human ovarian carcinoma cell line (2008) and its cisplatin-resistant variant (C13*).

Repair of cisplatin-damaged DNA was investigated in a human ovarian carcinoma cell line (2008) and its cisplatin-resistant variant (C13*) using a host-cell reactivation (HCR) assay. The HCR of cisplatin-damaged adenovirus (Ad) was not significantly different in C13* cells compared to 2008 cells. The cisplatin concentrations required to reduce the amount of viral DNA replicated to 50% were 0.12 +/- 0.02 microM and 0.10 +/- 0.01 microM after 48 h of repair in 2008 and C13* cells respectively. Similarly, the cisplatin concentration required to reduce the expression of a reporter gene inserted in the viral DNA was not significantly altered in C13* cells compared to the parental line (IC50 values were 0.28 +/- 0.04 microM in 2008 cells and 0.17 +/- 0.06 microM in C13* cells after 48 h of repair). Pretreatment of the cells with cisplatin, immediately prior to Ad infection, did not significantly alter the HCR of cisplatin-damaged Ad in either cell type. In addition, a cisplatin-sensitive variant derived from the C13* cells, namely the RH4 cells, did not differ significantly from either the 2008 or C13* cells in their ability to reactivate cisplatin-damaged Ad. Furthermore, a component of the nucleotide excision repair (NER) pathway, DNA polymerase alpha, was investigated using the competitive inhibitor aphidicolin. The combination of cisplatin and aphidicolin resulted in similar synergistic growth inhibition in both the 2008 and C13* cells providing additional support to the HCR results which suggest that enhanced NER is not responsible for the cisplatin resistance in C13* cells.

Adenoviridae↗
PubMed1994

Cross-resistance to cisplatin in cells resistant to photofrin-mediated photodynamic therapy.

This study shows that a Photofrin-induced photodynamic therapy-resistant variant (RIF-8A) of a radiation-induced fibrosarcoma-1 cell line (RIF-1) is cross-resistant to cis-diamminedichloroplatinum(II) (cisplatin). This is the first study to show cross-resistance to cisplatin in photodynamic therapy-resistant variants in vitro. Resistance does not appear to be the result of elevated glutathione levels since neither the resistant variant (RIF-8A) nor the parental line (RIF-1) varied in total glutathione levels. However, cisplatin-DNA adduct levels differed significantly between the two cell types. Immediately following a 1-h exposure to cisplatin (50 microM), RIF-1 cells contained 44.6 +/- 2.0 (SEM) pg platinum/micrograms DNA while RIF-8A cells contained 24.8 +/- 6.3 pg platinum/micrograms DNA. In addition, the resistant variant had decreased plasma and mitochondrial membrane potentials. The plasma and mitochondrial membranes of the resistant variant accumulated 3- and 3.6-fold less rhodamine 123, respectively. The difference in rhodamine 123 accumulation could not be attributed to elevated P-glycoprotein expression because both the parental line and the variant contained similar amounts of P-glycoprotein. In conclusion, alterations in the plasma and/or mitochondrial membrane potentials may provide cells with a survival advantage when challenged with either photodynamic therapy or cisplatin in vitro. This appears to be a novel mechanism of resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗