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DIVERSITY OF ARSENIC METABOLISM IN CULTURED HUMAN CANCER CELL LINES
Sharma, R, M Styblo, AND M J. Mass. DIVERSITY OF ARSENIC METABOLISM IN CULTURED HUMAN CANCER CELL LINES. Presented at NIEHS/NTA 3rd Annual Biomedical Science Fair, NIEHS, RTP, NC, April 28, 2000.
Diversity of arsenic metabolism in cultured human cancer cell lines.
Arsenic has been known to cause a variety of malignancies in human. Pentavalent As (As 5+) is reduced to trivalent As (As3+) which is further methylated by arsenic methyltransferase(s) to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). To date, arsenic methyltransferase(s) have been partiaIly purified from rabbit liver, but the amino acid or DNA sequences have not been obtained either in animal model or humans. The present studies were performed with the aim of eventuaIly finding a human cell line with enough intrinsic arsenic methytransferase activity such that it might be feasible to attempt isolation of this enzyme. We used several human cell lines originating from neoplasms of the liver (Hepatoblastoma, HepG2), lung (Non-smaIl ceIllung cancer, A549), kidney (Renal ceIl, UOK 109) and testis (Pluripotent embryonal ceIls, CRL-1973) to study the differential methylation of arsenic in these ceIls. Two million ceIls were exposed to 0.05,0.075, 0.1, 0.25 and 0.5 /lM concentrations of 73 As-sodium arsenite (5 /lCi) in 6-weIl plates for 48 hrs. The ceIl homogenate and media fractions were analyzed for inorganic arsenic, MMA and DMA by thin-Iayer chromatography. Tissue-specific differential methylation was observed in these studies. Among two metabolites, the formation of DMA (though not MMA) increased linearly upto 0.5 /lM in CRL-1973 and HepG2 ceIls. Among all the ceIl lines, CRL-1973 ceIl line, a testicular carcinoma, was the most efficient in methylating arsenic at 0.5 uM concentration as evident from DMA formation (DMA + MMA in pmols/106 ceIls /48 hr ; 181 + 18.69 for CRL-1973 ; 93.70+62.34 for HepG2 ceIls and 0 + 4.84 for A549 cells). However, DMA:MMA ratio was lower in HepG2 ceIls in comparison to CRL-1973 (CRL- 1973, HepG2, A549; 9.72:1; 1.5:1; 0:1). Although the cell lines used in this study are neoplasticaIly transformed and may not represent the normal methylation pattern, results indicate that testicular, hepatoblastoma and NSCLC ceIls methylated arsenic, but the renal cell carcinoma used was unable to methylate arsenic under these culture conditions.
This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL CARCINOGENESIS DIVISION
BIOCHEMISTRY AND PATHOBIOLOGY BRANCH