Submitted to: Cancer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/29/1995
Publication Date: N/A
Interpretive Summary: Glutathione is a naturally occurring compound found in all tissues. This compound is needed for cell function and growth. Because cancer is unregulated cellular growth, researchers have found that decreasing the amount of glutathione sensitizes (increases) a variety of cancer cells to agents used in chemotherapy. One method for decreasing cellular glutathione is to ingest or inject a synthetic compound, buthionine sulfoximine (BSO). BSO inhibits the cellular synthesis of glutathione. Because BSO has been proposed as a chemical that enhances the effectiveness of cancer treatment a study was undertaken to determine the effect of BSO in normal rat tissue. Female, young adult rats were injected with BSO twice daily for 7 days; control rats were injected with a saline solution. As expected, BSO treatment reduced cellular glutathione. More importantly, it was found that BSO treatment significantly decreased the plasma concentration of the hormones estradiol and progesterone. The results of the study suggest that this side effect (decreased estradiol and progesterone) has to be considered in the adjuvant BSO treatment of cancers in women.
Technical Abstract: Glutathione (GSH) is an important factor involved in resistance of tumor cells to anticancer agents. Buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, effectively decreases cellular GSH concentrations both in vitro and in vivo. Depletion of GSH by BSO sensitizes a variety of cancer cells to chemotherapeutic agents. Therefore, BSO has been on clinical trial as an anticancer adjuvant. For this purpose, it is important to understand the effect of BSO treatment not only on the sensitivity of tumor cells to anticancer agents, but also on metabolism and function of normal tissues. The present study was undertaken to determine the effect of BSO treatment on GSH concentrations in the blood, liver and ovary, and changes in concentrations of ovarian hormones and other important components in the plasma. Female Sprague- Dawley rats at age 90 days were treated with 2.0 mmol/kg BSO in saline by intraperitoneal injection, twice daily for 7 days. This treatment depressed GSH concentrations in the blood, liver and ovary by 95, 75, and 85%, respectively. A number of blood components were measured. BSO treatment significantly (p<0.01) elevated and lowered plasma concentrations of ceruloplasmin and urea nitrogen, respectively. More importantly, plasma concentrations of estradiol and progesterone were markedly (p<0.01) decreased in the BSO-treated animals. The results indicate that the side effect of BSO treatment on ovary function has to be considered when it is applied in the treatment of cancers in women.