Differential effect of cadmium on cholinephosphotransferase activity in normal and cancerous human mammary epithelial cell lines.
Cadmium (Cd) is an ubiquitous environmental carcinogen. Membrane phospholipids as well as fatty acid profile of membrane phospholipids are known to be altered in tumorigenicity and malignancy. Synthesis of cellular phosphatidylcholine (PC) has been used as a marker for membrane proliferation in the neoplastic mammary gland tissue. Cholinephosphotransferase (CPT), the terminal enzyme in de novo synthesis of PC, has an important role in regulating the acyl group of PC in mammalian cells. Our previous studies have shown that CPT is expressed differentially in the normal and cancerous mammary epithelial cell lines. In this study, we examined the effect of cadmium on CPT activity using normal (MCF-12A and MCF-12F) and cancerous (MCF-7, BT-549, and 11-9-1-4) human mammary epithelial cell lines. There was no consistent pattern of CPT activity in response to different doses of cadmium. The activity did not show a time-dependent variation at 5 micro M concentration, except in MCF-7 and 11-9-1-4. CPT gene expression increased with cadmium as evident from slot blots. Mutation in the nucleotide sequence was also observed as the result of cadmium but this did not result into amino acid sequence changes.
Department of Biochemistry and Department of Pharmacology, Meharry Medical College, Nashville, TN, USA. sdas@mmc.edu
Somdutta
S
Sinha Roy
Shyamali
S
Mukherjee
Sutapa
S
Mukhopadhyay
Salil K
SK
Das
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002104:Cadmium / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D048429:Cell Size; D002470:Cell Survival; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D016296:Mutagenesis / Q000187:drug effects
D002273:Carcinogens; D002104:Cadmium; D002798:Diacylglycerol Cholinephosphotransferase