Paper Information

Title: 

LACK OF A DIRECT CORRELATION BETWEEN THE TOTAL CELLULAR GLUTHATIONE LEVEL AND REDUCTION, WITH CISPLATIN CYTOTOXICITY IN THREE DIFFERENT HUMAN TUMOR CELL LINES

Type: SPEECH
Author(s): SHIRAZI FATEMEH,HOSSEINZADEH L.,TORSHABI M.
 
 
 
Name of Seminar: IRANIAN CONGRESS OF TOXICOLOGY
Type of Seminar:  CONGRESS
Sponsor:  SOCIETY OF TOXICOLOGY
Date:  2004Volume 8
 
 
Abstract: 

GLUTHATIONE (GSH) IS THE MOST ABUNDANT CELLULAR NON-PROTEIN THIOL, WHICH PARTICIPATES IN MANY IMPORTANT CELLULAR FUNCTIONS INCLUDING CYTOTOXIC-AGENTS DETOXIFICATION MECHANISMS AND CELLULAR AMINO ACID TRANSPORT. INCREASE IN THE CELLULAR GSH LEVEL HAS BEEN SHOWN IN SOME RESISTANCE CELL LINES TO ANTI-CANCER DRUGS. IT HAS BEEN SUGGESTED THAT THE ABILITY OF PLATINUM RESISTANT CELLS TO LIMIT DNA DAMAGE MAY OCCUR THROUGH THE DRUG CONJUGATION AND DETOXIFICATION WITH GSH IN SOME CELL LINES. IN THIS STUDY, WE ASSESSED AND COMPARED TOTAL GSH CONTENT OF THREE HUMAN TUMOR CELL LINES BEFORE AND AFTER ONE HOUR EXPOSURE TO THE IC50 CONCENTRATIONS OF CISPLATIN (CP). HUMAN OVARIAN SKOV3 CARCINOMA, HUMAN LUNG A549, AND HUMAN MELANOMA A375 CELLS WERE CULTURED IN DMEM/F12 MEDIA SUPPLEMENTED WITH 10% FETAL BOVINE SERUM, IN 37C HUMIFIED ATMOSPHERE CONTAINING 5% CO2, UP TO THE MID-LOGARITHMIC GROWTH. CISPLATIN IC50S OF THESE CELL LINES WERE MEASURED BY COLONOGENIC ASSAY AFTER ONE HOUR EXPOSURE OF CELLS TO THE DIFFERENT CONCENTRATIONS OF CLINICAL FORMULATION IN SERUM-FREE DMEM/F12 MEDIA. GLUTHATIONE CONTENT OF CELLS WAS DETERMINED AN HOUR AFTER EXPOSURE TO CP USING ELLMAN METHOD. CLONOGENIC ASSAY RESULTED IN IC50S OF 3.33, 10.5 AND 5.32UM FOR SKOV3, A549 AND A375 CELL LINES, RESPECTIVELY. THE RANK ORDER OF CP CYTOTOXICITY ON THESE CELL LINES WAS THEREFORE FOUND TO BE AS SKOV3>A375>A549. THE RANK ORDER OF CELLULAR CONCENTRATION OF GSH IN THE CONTROL POPULATION OF THESE CELL LINES WAS FOUND TO BE AS SKOV3> A549 > A375. OUR RESULTS SHOWED THAT THE GSH CONTENT OF ALL CELL LINES DECREASED AFTER EXPOSURE TO CP. CELLULAR GSH LEVEL OF SKOV3 CELL LINE RESULTED IN THE MOST SIGNIFICANT DECREASE BY 34.91% REDUCTION. HUMAN LUNG A549 CELL LINE GSH LEVEL HAS ALSO BEEN DECREASED BY …%. HOWEVER, WE DID NOT FIND ANY SIGNIFICANT DECREASE IN THE CELLULAR LEVEL OF GSH OF MELANOMA CELL LINE AFTER THE EXPOSURE TO CP IN THIS PERIOD OF TIME. AS A RESULT, THE RANK ORDER OF REDUCTION IN CELLULAR GSH AFTER ONE HOUR EXPOSURE TO CP WAS FOUND TO BE SKOV3>A549>A375. IN CONCLUSION, IN SPITE OF SOME PREVIOUS THOUGHTS IN THE IMPORTANCE OF GLUTATHIONE IN CP CYTOTOXICITY, OUR EXPERIMENTS WAS NOT ABLE TO PRESENT ANY DIRECT CORRELATION BETWEEN THE BASAL LEVEL OF CELLULAR GSH, OR ITS REDUCTION AFTER EXPOSURE TO CISPLATIN, WITH THE DEGREE OF SENSITIVITY OR RESISTANCE TO THIS DRUG. OUR RESULTS SUGGEST THE PRESENCE OF SOME OTHER IMPORTANT CELLULAR FACTORS, WHICH MIGHT AFFECT THE DIRECT CORRELATION BETWEEN CELLULAR GSH AND CELLULAR SENSITIVITY OR RESISTANCE TO CISPLATIN. FURTHER STUDIES TO EXPLORE THOSE OTHER PARAMETERS WHICH ARE IMPORTANT IN THE CYTOTOXICITY OF PLATINUM COMPOUNDS IN THESE CELL LINES ARE RECOMMENDED.

 
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