An assessment of the risks of carcinogenicity associated with polyhydroxyalkanoates through an analysis of DNA aneuploid and telomerase activity.
Polyhydroxyalkanoates (PHA) are aliphatic polyesters synthesized by many bacteria. Because of their flexible mechanical strengths, superior elastic property, biodegradability and biocompatibility, PHA have been developed for applications as medical implants, drug delivery matrices, and devices to support cell growth. Lots of studies showed that PHA matrices improved cell proliferation and tissue regeneration. However, the possibility of whether rapid cell proliferation on PHA matrices will induce tumor formation is unclear. Here we confirmed that proliferating rat osteoblasts grown on films of various PHA including PHB, PHBV, P3HB4HB, PHBHHx and PHBVHHx did not lead to cancer induction at least for p8th. Cell proliferation was evaluated by the incorporation of 5-bromodeoxyuridine (BrdU), the transcript expression of cancer related genes Ki67, p53 and c-Fos was monitored by quantitative Real-time PCR, the results showed the cells proliferating on the PHA films were under normal cell cycle regulation. Moreover, DNA aneuploid and telomerase activity were only detected in the positive control UMR-108 cells; compared with cells grown on films, UMR-108 cells had longer telomeres, further demonstrated the normal status of cells proliferating on the PHA films. It indicated that the above PHA family members could be used to support cell growth without indication of susceptibility to tumor induction. These results will be important for promoting the application of PHA as new members of biomaterials.
Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China.
Si-Wu
SW
Peng
Xiao-Yong
XY
Guo
Guan-Guan
GG
Shang
Jian
J
Li
Xian-Yi
XY
Xu
Ming-Liang
ML
You
Ping
P
Li
Guo-Qiang
GQ
Chen
D000782:Aneuploidy; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D015197:Carcinogenicity Tests; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000235:genetics*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D011091:Polyesters; D054813:Polyhydroxyalkanoates / Q000737:chemistry / Q000633:toxicity*; D011108:Polymers / Q000737:chemistry; D000091402:Prohibitins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism
C000717328:PHB protein, human; C000717332:Phb protein, rat; D011091:Polyesters; D054813:Polyhydroxyalkanoates; D011108:Polymers; D000091402:Prohibitins; D012333:RNA, Messenger; D019344:Lactic Acid; C033616:poly(lactide); D004247:DNA; D019098:Telomerase; D001973:Bromodeoxyuridine