Purpose:Folate deficiency and reduced DNA repair capacity are established risk factors for squamous cell carcinoma of the head and neck(SCCHN). We hypothesized that polymorphisms of the thymidylate synthase(TYMS)gene,which regulates a key enzyme in folate metabolism required for DNA synthesis and repair, are associated with SCCHN risk. Experimental Design:In a hospital-based case-control study of 704 SCCHN cases and 1,085 controls, frequency matched by age,sex, nd ethnicity,we genotyped the TSER(thymidylate synthase in the 5'-untranslated enhanced region)and TS3ˊUTR(thymidylate synthase in the 3'-untrans-lated region) polymorphisms. Results: The TS3ˊUTR 0bp/0bp genotype was associated with a significantly decreased risk of SCCHN[adjusted odd ratio(OR)=0.67,95%confidence interval (CI)=0.47-0.94] compared with the 6bp/6bp genotype, but the TSER polymorphism had no main effect on risk of SCCHN. When we evaluated the two polymorphisms together by the number of protective alleles(the TSER 3R and TS3'UTR 0bp alleles), we found that the combined genotypes with four protective alleles(the TSER 3R3R and TS3'UTR 0bp/0bp) was associated with significantly decreased SCCHN risk (OR=0.60, 95%CI=0.37-0.98). In addition,the TS3ˊUTR 0bp genotypes were associated in an allele dose-dependent manner with a decreased risk of overall stage IV oral cancer (OR=0.84, 95%CI=0.52-1.34 for the 6bp/0bp genotype and OR=0.26, 95%CI=0.08-0.87 for the 0bp/0bp genotype; Ptrend=0.035). Conclusion: The TSER and TS3'UTR polymorphisms are associated with SCCHN risk. The TSER 3R and TS3ˊUTR 0bp alleles seemed to jointly protect against SCCHN. In particular, the 0bp allele seemed to protect against oral cancer progression.

The present study was to investigate whether metallothionein(MT)was involved in sensitivity of testis to cadmium (Cd) and protection of rats from Cd-induced testis damages.The rats were treated by intraperitoneal injection with 0.2,0.4,and 0.8mgCd/kg BW for 7days.The atomic absorption spectrophotometry and cadmium hemoglobin affinity assay were applied to evaluate the contents of Cd and MT in testis and liver.The testis glutathione(GSH),malondialdehyde(MDA)and daily sperm production were measured.There were substantial increases of both Cd and MT in the liver after Cd exposure.The testis Cd and MT contents were lower than those in the corresponding liver in Cd-exposed rats.Low doses of Cd (0.2and0.4 mg/kgBW) induced MT in testis,while a significant decline of MT was found in rats treated with 0.8mgCd/kgBW. By a concomitant decrease of MT,there was an obvious increase of MDA and marked decreases of GSH,daily sperm production in rats treated with 0.8mgCd/kgBW.These findings suggested MT was more difficult to be induced in the testis than in the liver by Cd,which might account for the high susceptibility of testis to Cd.MT, increased by a low dose of Cd,played an important role in protecting testis against Cd toxicity by sequestering and antioxidating.

Aims: To determine sperm nuclear DNA integrity and to investigate the relation between fenvalerate(FE)exposure and spermatozoa DNA damage. Methods: Sperm DNA fragmentation was detected by a modified alkaline single cell gel electrophoresis (Comet) assay and a terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay. The olive tail moment (OTM) and percentage tail DNA were measured by the Comet assay, and cell positive percentage was measured by the TUNEL assay for DNA damage evaluation. Results: he DNA integrity of spermatozoa of external and internal control groups were both significantly greater than that of the FE exposed group. The median value of tail DNA percentage in the exposure group was 11.30, which was significantly higher than 5.60 in the internal control group and 5.10 in the external control group. The median value of OTM was 3.80 in the exposure group, significantly higher than 1.50 in the internal control group and 2.00 in the external control group.Mean cell positive was 31.2% in the exposure group, significantly higher than 17.4% in the internal control and 19.6% in the external control groups.Cell positive (%) was significantly correlated with tail DNA percentage and with OTM of whole subjects (n=63). Conclusions:Results showed that occupational FE exposure is associated with an increase in sperm DNA damage.A combination of the Comet and TUNEL assays would offer more comprehensive information for a better understanding of sperm DNA damage,and the biological significance of sperm DNA damage in sperm function and male infertility.

The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined.Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU)(20mg/kg b.w.ip) twice a week for 4 weeks,then given basal diet containing 5% TPA,5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1%TPA for the next22weeks, and then euthanized. 5%TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate.Though 5% TPA plus 4% Sodium bicarbonate(NaHCO3)and 1% TPA treatment did not induce urinary bladder calculi formation,they resulted in a moderate increase in urinary precipitate.Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia,papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control.MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia(not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (Ca TPA) may also have weak promoting activity on urinary bladder carcinogenesis.

Carbaryl, one of the most important insecticides,is widely produced and used. To explore carbaryl-induced genotoxic effects of spermatozoa, particularly DNA damage and chromosome aberrations(CA),we firstly examined conventional semen parameters, the progression and motion parameters of the spermatozoa among 16 carbaryl-exposed workers and 30 internal and external control individuals.Sperm DNA damage represented as positive percentage of DNA fragmentation was detected by a modified terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay.Then numerical CA of chromosome X,Y and 18 were investigated by multicolor fluorescence in situ hybridization (FISH). The results showed significant differences in the percentage of sperm abnormality between carbaryl-exposed group and the external control group (P=0.008). Mean (