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Biomedical subjects

R G Best

Publications and source records attributed to R G Best.

21 records · Page 2Linked to original sources

Sister chromatid exchange in human lymphocytes exposed to ascorbic acid and the cancer chemotherapeutic agent 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

This study examines sister chromatid exchange (SCE) induction by ascorbate, a weak in vitro SCE inducer which acts through free radical intermediates, and low doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), a potent SCE inducer which acts primarily through DNA interstrand cross-links. A small dose-dependent increase in SCE was observed in human peripheral lymphocytes exposed to ascorbate in the 0.5-10 mM dose range for 59 hours, with significant slowing of cell cycle kinetics at concentrations at and above 5 mM. CCNU concentration was selected to approximate the maximal increase in SCE induced by ascorbate. SCE frequencies in cells exposed sequentially to both agents were not significantly different from expectations under an additivity-of-effect model based on SCE response to each agent individually. Despite clear differences in the types of lesions induced, ascorbate and CCNU appear to act independently to induce SCE in a manner consistent with, though not exclusive to, Painter's replicon cluster model.

Adult↗

Variable sister-chromatid exchange response in human lymphocytes exposed in vitro to gossypol acetic acid.

Gossypol has potential for widespread use as a male oral antifertility agent in humans since it appears to be highly efficacious, with reversible spermatostatic effects and minimal side effects. Furthermore, it is both inexpensive and readily available. Therefore, a thorough understanding of gossypol's genotoxic potential is critical. Although genotoxicity studies have produced conflicting reports, increased sister-chromatid exchange (SCE) and DNA-strand breaks have been reported in human cells exposed to gossypol in vitro. In the present study, SCE was examined in purified human lymphocytes and whole blood cultures exposed to gossypol acetic acid at various concentrations in serum-free medium. A small but statistically significant increase in SCE was observed in pooled analysis of 7 donors in whole blood cultures exposed to 0.70 microM gossypol acetic acid (p less than 0.02). Individual analyses revealed only one donor with a significant SCE response (p less than 0.001). In subsequent experiments, exposure at higher doses had no effect on SCE frequencies. A small but significant increase in SCE was observed in ficoll/hypaque purified lymphocytes exposed to 0.07 and 0.70 microM gossypol acetic acid. Interpretation of SCE data with variable response is discussed.

Cells, Cultured↗

Chromosomal abnormalities in ectopic pregnancy chorionic villi.

OBJECTIVE: To evaluate the incidence of chromosomal abnormalities in ectopic pregnancy chorionic villi. METHODS: A prospective study of patients with the diagnosis of ectopic pregnancy was conducted, with chorionic villi obtained at the time of surgical therapy cultured and analyzed for karyotype. Review of the patient's medical record and ultrasound evaluation was then completed and findings correlated with karyotype results. RESULTS: Twenty-two patients undergoing surgery for the diagnosis of ectopic pregnancy yielded chorionic villi for culture. Successful culture was performed in 21 patients, with 3 (14%) revealing abnormal karyotypes. Review of the medical record showed ultrasound results consistent with fetal development or a gestational sac in 15 of 18 patients with normal chromosomal analysis. Three of 6 patients without fetal development yielded abnormal chromosomal findings. CONCLUSION: Our results confirm that a high degree of success can be achieved in the karyotype analysis of ectopic pregnancy chorionic villi and that these conceptuses have a rate of abnormality similar to that reported for intrauterine gestations. Our data further suggest that when a gestational sac or fetal pole is identified by ultrasound, there is usually a normal karyotype.

Chorionic Gonadotropin, beta Subunit, Human↗