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Studies on the tumor-promoting activity of biomaterials: inhibition of metabolic cooperation by polyetherurethane and
T Tsuchiya1, H Hata, A Nakamura
1National Institute of Health Sciences, Tokyo, Japan.
Abstract:
When V79 metabolic cooperation (MC) assay was performed to detect tumor-promoting activities, inhibitory activities on the gap-junctional intercellular communication were first detected in both extracts prepared from polyetherurethane (PEU) and silicone. The former inhibited more strongly than the latter. Furthermore, the lowest effective concentrations in MC assay correlated well with the values of the total active incidences obtained by histologic evaluation of the 2-year implantation test in rats. Poly(tetramethylene oxide) (PTMO) showed the highest inhibitory activities among the constituents of PU. Thus, the shorter the chain length of PTMO, the stronger the inhibitory activities of PTMO in MC assay. PTMO moiety may play an important role in the tumor-promotion stage during tumorigenesis induced by PU.
Insights
Polyetherurethane (PEU) and silicone extracts inhibit gap-junctional intercellular communication, suggesting tumor-promoting activity. Shorter poly(tetramethylene oxide) (PTMO) chains in PEU showed stronger inhibition, highlighting PTMO
Area of Science:
- Biomaterials Science
- Toxicology
- Cancer Research
Background:
- Polyurethane (PU) and silicone are widely used biomaterials.
- Tumorigenesis involves complex cellular processes, including intercellular communication.
- Assessing biomaterial-induced tumor promotion is crucial for safety.
Purpose of the Study:
- To investigate the tumor-promoting potential of polyetherurethane (PEU) and silicone extracts.
- To evaluate the role of gap-junctional intercellular communication (GJIC) in biomaterial-induced tumorigenesis.
- To identify specific chemical moieties responsible for tumor promotion.
Main Methods:
- V79 metabolic cooperation (MC) assay to detect inhibition of GJIC.
- Histologic evaluation of 2-year implantation tests in rats.
- Analysis of chemical constituents, specifically poly(tetramethylene oxide) (PTMO).
Main Results:
- Both PEU and silicone extracts inhibited GJIC in the MC assay.
- PEU extracts exhibited stronger inhibitory activity than silicone extracts.
- PTMO, a constituent of PU, showed the highest inhibitory activity, with shorter chain lengths being more potent.
- Inhibitory concentrations in the MC assay correlated with tumor incidence in implantation tests.
Conclusions:
- PEU and silicone possess tumor-promoting activities, evidenced by GJIC inhibition.
- PTMO moiety is a key factor in the tumor-promotion stage of PU-induced tumorigenesis.
- The MC assay is a valuable tool for predicting the tumor-promoting potential of biomaterials.