Cervical cancer is a leading cause of cancer-related deaths in developing countries, and the human papillomavirus (HPV) is linked etiologically to cervical cancer. Eighty nine cervical carcinoma biopsies collected from women visiting the Oncologic Center in Casablanca (Centre Hospitalier Universitaire Ibn Rochd, Morocco) for cervical cancer symptoms, were screened for HPV DNA by polymerase chain reaction amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 45, and 59. Using very high stringency hybridization the HPV types could be easily distinguished. After preliminary clinical sorting, 92% (82/89) of the samples were found to be HPV-positive. Among the samples infected by a single HPV, type 16 was the most frequent 36.6% (30/82) of the positive samples, followed by HPV 18; 19.5% (16/82). Double or even multiple infections by the different HPV types were also detected (35.5% of the positive samples); dual infections were the more frequent, with the following combinations of HPVs: HPV16/HPV18 (21% of the positives samples) and HPV16/HPV45 (8.5%).

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Doxorubicin‐induced lipid peroxidation was evaluated in four human or murine cell strains in culture and in their doxorubicin‐resistant variants, by the quantification of malondialdehyde produced after a 2‐h incubation of cells with the drug. Significantly increased malondialdehyde levels were obtained 24 h after doxorubicin treatment in three of the wild‐type cell lines with doses as low as 0.05–0.1 μg/ml, which is within an order of magnitude of the concentration of the drug which inhibits cell growth by 50%. This production of malondialdehyde was abolished in two doxorubicinresistant strains, even with high doses of drug (100–300 μg/ml), but was maintained in the third resistant line. No malondialdehyde production was observed in the fourth cell line, sensitive or resistant. It is remarkable that an enhancement of selenium‐dependent and non‐selenium‐dependent glutathione peroxidase activities was exhibited during the acquisition of resistance to doxorubicin in the two first lines, but not in the third, whereas a constitutively high non‐selenium‐dependent glutathione peroxidase activity existed in the doxorubicin‐sensitive and doxorubicin‐resistant variants of the fourth cell line. Gene expression of selenium‐dependent glutathione peroxidase and of glutathione S‐transferase π, which is known partially to bear a non‐selenium‐dependent glutathione peroxidase activity, were correlated with the corresponding enzyme activities. It appears, therefore, that the already known enhancement of glutathione peroxidase activity and expression in doxorubicin‐resistant cell lines has a quantifiable consequence upon doxorubicin‐induced lipid peroxidation and may have consequences in the mechanism of resistance to this drug.

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We have studied the formation of hydroxyl radical (OH') induced by doxorubicin in a series of doxorubicin-or vincristine-selected variants of C6 rat glioblastoma cells in culture by electron-spin resonance spectroscopy using 5,5'-dimethyl-1-pyrroline-l-oxide as a spin trap. Wild-type cells, sensitive to doxorubicin, exhibited in the presence of this drug a concentration-dependent OH' formation which could be inhibited by preincubation with superoxide dismutase, catalase or an antibody against cytochrome P450-reductase. In highly doxorubicin-resistant cells, OH' formation was reduced to about 20% of the level obtained in sensitive cells. In cells presenting a very low level of resistance to doxorubicin or in cells selected with vincristine, both presenting a pure multidrug-resistant phenotype, OH' formation was identical to that obtained in sensitive cells. In cells of intermediate resistance or in revertant cells, intermediate levels of OH' formation were obtained. Protection against OH' formation and action can be identified at the levels of superoxide dismutase and glutathione peroxidase activities, which are both enhanced in the resistant cells.

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We have studied the formation of hydroxyl radical (OH•) induced by doxorubicin in a series of doxorubicin‐ or vincristine‐selected variants of C6 rat glioblastoma cells in culture by electron‐spin resonance spectroscopy using 5,5′‐dimethyl‐1‐pyrroline‐1‐oxide as a spin trap. Wild‐type cells, sensitive to doxorubicin, exhibited in the presence of this drug a concentration‐dependent OH• formation which could be inhibited by preincubation with superoxide dismutase, catalase or an antibody against cytochrome P450‐reductase. In highly doxorubicin‐resistant cells, OH• formation was reduced to about 20% of the level obtained in sensitive cells. In cells presenting a very low level of resistance to doxorubicin or in cells selected with vincristine, both presenting a pure multidrug‐resistant phenotype, OH• formation was identical to that obtained in sensitive cells. In cells of intermediate resistance or in revertant cells, intermediate levels of OH• formation were obtained. Protection against OH• formation and action can be identified at the levels of superoxide dismutase and glutathione peroxidase activities, which are both enhanced in the resistant cells.