Genotoxic properties of materials used for endoprostheses: Experimental and human data.

Approximately 2 million endoprostheses are implanted annually and metal ions as well as particles are released into the body from the materials which are used. This review describes the results of studies concerning genotoxic damage caused by artificial joints. DNA damage leads to various adverse long-term health effects in humans including cancer. Experiments with mammalian cells showed that metal ions and particles from orthopedic materials cause DNA damage. Induction of chromosomal aberrations (CA) was found in several in vitro experiments and in studies with rodents with metals from orthopedic materials. Human studies focused mainly on induction of CA (7 studies). Only few investigations (4) concerned sister chromatid exchanges, oxidative DNA damage (2) and micronucleus formation (1). CA are a reliable biomarker for increased cancer risks in humans) and were increased in all studies in patients with artificial joints. No firm conclusion can be drawn at present if the effects in humans are due to oxidative stress and if dissolved metal ions or release particles play a role. Our findings indicate that patients with artificial joints may have increased cancer risks due to damage of the genetic material. Future studies should be performed to identify safe materials and to study the molecular mechanisms in detail.

[Biomechanical research on upper femur with vertical and bending stress].

OBJECTIVE: To study the bone state with ultimate stress by examining biomechanical distribution of upper femur in Chinese, in order to accumulate more experiences for clinical work. METHODS: Totally 60 Chinese femurs from fresh cadavers were randomly divided into two groups. All the femurs were cleaned, and the body age ranged from 36 to 72 years old, averaged 56.4 years, including 41 from males, and 19 from females. These two groups underwent mechanical stress and bending stress tests. Special mechanical laboratory and machines were used to get the information. Results about the loading value at each testing point under stress were collected. RESULTS: The four faces of the upper femur suffered different stress under external forces. The bone on upper femur can tolerate more mechanical stress than bending stress. Medial and lateral region of the femur neck and the rear side of the small tuberosity section were themain position enduring the vertical stress. The rear position of the base femur neck and the small tuberosity section were the main regions enduring the bending stress. Those main positions had strong cancellous bones. The intertrochanteric fracture fixation and artificial femoral stems were designed depending on this biomechanical basis. CONCLUSION: According to our experiment result, doctors need to chose more effective fixations for upper femur fracture, and femoral stems for the patients. More information should be collected by further researches.

[Analysis on morphology and stability of femoral hip prosthesis based on the revision operation].

OBJECTIVE: According to the information obtained from the revision of total hip arthroplasty, the situations of the artificial femoral stem under physiological stress were analyzed preliminarily. In order to accumulate clinical experience, the discussions about how to enlongate the life of artifical joints were performed. METHODS: Fifty-three patients required revision operations were selected, including 28 males and 25 females,with an average age of 74.66 years old (61 to 84 years old). The average life of artificial joints was 18.24 years (3 to 27 years). The initial weightbearing was started 11 days (5 to 16 days) after the first operation. The main reasons for the revision were the spontaneous loosening and trauma. Based on imaging and surgical findings, as well as the histological pathology, the situations of the stems in human bodies were determined. RESULTS: Femoral prosthesis would sink under physiological stress. The design of femoral stems, motion of patients', and bone growth determined the secondary stability. Straight stems were helpful for physiological subsidence of prosthesis, achieving the stability with close bone-implant contact by bone growth,which allowed the patient to do early landing exercise. The collared prosthesis and prosthesis combined with internal fixation limited the subsidence of femoral stems. Their stability depends on the time of initial placement and the bone growth for supporting. Delaying the inital weightbearing was suggested for patients with these protheses. CONCLUSION: According to the actual situation of the patients, the appropriate chosen of femoral stems and time to perform the weightbearing can extend the life of the femoral prosthesis.

[Construction and identification of small interfering RNA expression plasmid targeting Sox9 and the function to cell growth and apoptosis of human chondrosarcoma cells HTB94].

OBJECTIVES: To construct small interfering (siRNA) Sox9 expression plasmid and transfer it into human chondrosarcoma cells HTB-94, and to check the mRNA and protein expression of Sox9 and cell growth and apoptosis of HTB-94 human chondrosarcoma cells. METHODS: siRNA(Sox9) expression plasmid was designed and synthesized. And it was transferred into HTB-94 human chondrosarcoma cells. Then the expression of the mRNA and protein of Sox9, cell growth and apoptosis in transferred HTB-94 human chondrosarcoma cells were checked. RESULTS: The recombinant plasmid was confirmed by enzyme digestion analysis and DNA sequencing. The expression of the mRNA and protein expression of Sox9 in transferred HTB-94 were significantly reduced. The cell growth of HTB-94 was inhibited, and the apoptosis of HTB-94 was remarkably increased. CONCLUSION: siRNA (Sox9) expression plasmid could be transferred into HTB-94 human chondrosarcoma cells. And it can reduce the mRNA and protein expression of the HTB-94, inhibit the cell growth and cause the apoptosis of the tumor cells.

Response of isolated hepatocytes from carcinogen sensitive (C3H) and insensitive (C57BL) mice to signals inducing replication or apoptosis.

The mouse strain C3H shows high incidence of liver tumors in carcinogenicity testing, while the strain C57BL exhibits low incidence. The F1 generation hybrids, B6C3F1, which are widely used in long-term carcinogenesis bioassays, are of intermediate sensitivity. We asked whether this strain difference could be due to different susceptibility of the parenchymal cells to signals inducing replication or apoptosis. Hepatocytes were isolated and cultured according to standard protocols. We tested (1) for the induction of DNA synthesis by epidermal growth factor (EGF), (2) for its inhibition by TGF-beta1, and (3) for the induction of apoptosis by TGF-beta1. Basal rates of DNA synthesis in untreated hepatocytes cultured from C3H and B6C3F1 mice were 6.5 and 3.5 times higher, respectively, than in hepatocytes from C57BL on day 3. Moreover, addition of EGF (10 ng/ml) increased DNA synthesis on day 3 in hepatocytes from C3H (4.2-fold) and B6C3F1 (2.7-fold) more strongly than in hepatocytes from C57BL. Treatment with TGF-beta1 inhibited basal and EGF-stimulated DNA synthesis dose-dependently. Inhibition was maximal at 1 ng TGF-beta1/ml in cultures from C57BL mice, and at 0.3 ng/ml in hepatocytes from C3H mice. In untreated hepatocytes from both strains virtually no apoptotic figures (condensed or fragmented nuclei, Hoechst 33285 staining) were found. After treatment with TGF-beta1 the incidence of apoptotic nuclei in hepatocytes from C57BL was higher than in cells from C3H mice (1.7% vs 3% on day 3). Thus it appears that hepatocytes from C57BL mice possess a lower growth potential, as indicated by a low basal rate of DNA synthesis and low inducibility by EGF, but a higher sensitivity to induction of apoptosis by TGF-beta1 than hepatocytes of the C3H strain. These findings may be helpful to explain the different susceptibility to induction of hepatocarcinogenesis in C3H and C57BL mice.

Chemoprotective effects of garden cress (Lepidium sativum) and its constituents towards 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ)-induced genotoxic effects and colonic preneoplastic lesions.

The chemoprotective effect of garden cress (GC, Lepidium sativum) and its constituents, glucotropaeolin (GT) and benzylisothiocyanate (BITC), a breakdown product of GT, towards 2-amino-3-methyl-imidazo [4,5-f] quinoline (IQ)-induced genotoxic effects and colonic preneoplastic lesions was investigated in single cell gel electrophoresis (SCGE) assays and in aberrant crypt foci (ACF) experiments, respectively. Pretreatment of F344 rats with either fresh GC juice (0.8 ml), GT (150 mg/kg) or BITC (70 mg/kg) for three consecutive days caused a significant (P < 0.05) reduction in IQ (90 mg/kg, 0.2 ml corn oil/animal)-induced DNA damage in colon and liver cells in the range of 75-92%. Chemical analysis of GC juice showed that BITC does not account for the effects of the juice as its concentration in the juice was found to be 1000-fold lower than the dose required to cause a chemoprotective effect. Parallel to the chemoprotection experiments, the modulation of the activities of cytochrome P4501A2, glutathione-S-transferase (GST) and UDP glucuronosyltransferase (UDPGT) by GC juice, GT and BITC was studied. Whereas GT and BITC did not affect the activity of any of the enzymes significantly, GC juice caused a significant (P < 0.05) increase in the activity of hepatic UDPGT-2. In the ACF assay, IQ was administered by gavage on 10 alternating days in corn oil (dose 100 mg/kg). Five days before and during IQ treatment, subgroups received drinking water which contained 5% cress juice. The total number of IQ-induced aberrant crypts and ACF as well as ACF with crypt multiplicity of > or =4 were reduced significantly (P < 0.05) in the group that received IQ plus GC juice compared with the group that was fed with IQ only. However, crypt multiplicity was not significantly different in these two groups when all ACF with all classes of crypt multiplicity were considered in the analysis. This is the first report on the inhibition of HA-induced DNA damage and preneoplastic lesions by a cruciferous plant. Our findings suggest that the chemoprotective effect of GC is mediated through enhancement of detoxification of IQ by UDPGT.