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Gene expression changes in BALB/3T3 transformants induced by poly(L-lactic acid) or polyurethane films
Atsuko Matsuoka1, Toshie Tsuchiya
1Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. matsuoka@nihs.go.jp
Journal of Biomedical Materials Research. Part A
|January 6, 2004
Summary
Polyurethane (PU) and poly(L-lactic acid) (PLLA) films induced cancer-related gene expression changes in BALB/3T3 cells. PLLA films induced more malignant transformants with significant bone formation gene alterations.
Area of Science:
- Biotechnology
- Genomics
- Oncology
Background:
- Biomaterials like polyurethane (PU) and poly(L-lactic acid) (PLLA) are used in medical applications.
- Cellular transformation and tumor formation are critical safety concerns for implanted biomaterials.
- Understanding the molecular mechanisms underlying material-induced carcinogenesis is essential.
Purpose of the Study:
- To investigate the gene expression profiles of BALB/3T3 cells transformed by PU and PLLA films.
- To identify cancer-related genes altered during the transformation process.
- To correlate gene expression changes with the transforming ability and malignancy of the cells.
Main Methods:
- DNA microarray analysis was performed on BALB/3T3 transformants induced by PU and PLLA films, alongside parental cells.
- Gene expression levels of cancer-related genes were quantified and compared across different cell lines.
- The transforming ability and malignancy of cell lines were assessed and correlated with gene expression data.
Main Results:
- A total of 1176 cancer-related genes were found to be differentially expressed in at least one transformant.
- Key genes such as c-fos, FBJ osteosarcoma oncogene B, and Jun were markedly up-regulated.
- Pleiotrophin, histidine triad nucleotide-binding protein, protein kinase C iota, and large multifunctional protease 7 were markedly down-regulated.
- A common functional theme among significantly altered genes was bone formation, consistent with observed tumor formation in rats.
- Poly(L-lactic acid) (PLLA) induced more malignant transformants than polyurethane (PU), particularly showing osteosarcoma-like gene expression.
Conclusions:
- Biomaterial implantation, specifically PLLA and PU films, can induce significant cancer-related gene expression changes in cells.
- The extent of gene expression alteration correlates with the malignancy of the transformed cells.
- The observed bone formation-related gene expression changes may be linked to the tumorigenic potential of these biomaterials.