aphidicolin and Uterine-Cervical-Neoplasms

Blood samples were obtained from 80 women: Twenty of these samples were from women affected by ductal infiltrating breast carcinoma, twenty from women affected by cervix uterine cancer, and forty individuals were screened for a control group. The search for chromosome instability that is known to affect individuals with cancer was performed through chromosome analysis in nontumor cells, intending to establish frequency and different types of numerical and structural aberrations. The results, in regard to spontaneous and aphidicolin induced chromosome aberrations, showed a significantly greater frequency (p < 0.001) of chromosome fragility, as well as other numerical and structural aberrations in breast cancer patients when compared to the control group. Similar results were obtained from cervix uterine cancer patients with the exception of certain numerical aberrations in which no significant differences were found. This suggests the existence of a certain degree of chromosomal instability affecting individuals with both types of cancer. The increase in fragility may play an important role in the biologic behavior and progression of cancer.

Topics: Adult; Aged; Aphidicolin; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Squamous Cell; Chromosome Aberrations; Chromosome Fragility; Chromosomes; DNA Repair; Enzyme Inhibitors; Female; Humans; Middle Aged; Nucleic Acid Synthesis Inhibitors; Uterine Cervical Neoplasms

The in vitro cell survival of a human cervix carcinoma cell line (HX156c) has been assessed using 60Co gamma-rays administered at either high (150 cGy/min) or low (3.2 cGy/min) dose rate. Recovery during low dose-rate irradiation was observed; the dose reduction factor at 10(-2) cell kill for 150 versus 3.2 cGy/min was around 1.3. An insight into the possible underlying mechanisms of this recovery process has been investigated by addition of non-toxic concentrations of various agents thought to inhibit eukaryotic DNA repair. Agent were added 2 h prior to irradiation and removed after 24 h exposure. Differential effects among the inhibitors were observed; aphidicolin had no effect on cell survival, novobiocin, hydroxyurea and 3-aminobenzamide reduced survival by a similar extent at both dose rates, beta-ara A and caffeine reduced survival to a greater extent during low dose-rate irradiation. beta-ara A and caffeine seemed to exert their effects mainly by increasing the alpha component of the acute survival curve. Since survival curves obtained at dose rates of around 3 cGy/min help define a dominant component of the initial slope of the acute curve we have demonstrated that beta-ara A and caffeine modify the initial slope, probably by inhibiting DNA repair processes involved in the sparing of tumour cells during protracted irradiation.

Topics: Aphidicolin; Benzamides; Caffeine; Cell Line; Cobalt Radioisotopes; Diterpenes; DNA Repair; Female; Humans; Hydroxyurea; In Vitro Techniques; Novobiocin; Radiation Dosage; Tumor Cells, Cultured; Uterine Cervical Neoplasms; Vidarabine