The blood radioactivity-time curve after iv [3H] CMCa in S180 bearing mice was found to be diexponential model.Pharmacokinetic parameters; t1/2 ?=9.6min, t1/2 P=37 h.It was quite rapidly distributed from the central compartment to the peripheral compartment.The highest radioactivity and the slowest metabolic rate were found in tumor.It further confirmed our foregoing result that this drug could concentrate in tumor,and was lower in brain with decreased neurotoxicity.The metabolic rates of the drug in blood and muscle were quite rapid, indicating it might be useful for clinical diagnosis and therapy of tumor.The results analyzed by TLC and scintillation counting of urine taken 24 h after iv [3H] CMCa to S180 bearing mice indicated that approximately 80% of urine total radioactivity was excreted as original drug in unchanged form and 7% as its hydrolyzate metronidazol.These results were similar to those in normal mice.

This paper compares the radiosensitizing effect of metronidazole(M) with that of its derivatives(CM)on sarcoma 180 (S180).After i.p injection S180 bearing mice were either irradiated with y-ray 17Gy or unirradiated under aerated or tumor acute local hypoxic conditions.Results indicate that under hypoxic condition tumor growth Was inhibited within 10 d after a single i.p injection of drugs, but under aerated condition inhibition of tumor growth did not occur.CM was found to be stronger than M in tumor inhibiting effect.After aerated irradiation the drug groups demonstrated an apparent slowing down of tumor growth.But the difference between groups was not obvious.Hypoxic irradiation produced a very strong inhibiting effect in the drug groups.CM, especially when it was chelated with Ca++to form CMCa, was strongest in tumor growth inhibition.Its tumor inhibiting ratio was 77.4%, enhancement ratio(ER)2.46 and sensitizing enhancement ratio(SER)1.89.Its tumor inhibiting effect was stronger than irradiation without drug administration and irradiation after the administration of M.Its radiossnsitizng effect was found to be twice stronger than that of the original compound(M), but its toxic side effect was slighter than M.

The induction of DNA single-strand breaks(ssb)by exposure to hematoporphyrin photosensitizer(PSD-007)followed by photoirradiation was observed in mice leukemia cells(L7712)in vitro. DNA ssb increased with the increase of dose of light in the rangeof 6.3-21 J/cm2 after treatment with 30?g/ml PSD-007. In lower concentration(1?g/ ml)of the drug,no ssb could be estimated after light exposure. Whan the concentration of PSD-007 was increased from 10 to 30?g/ml, however, the amount of ssb showed a rapid increase and tend to reach a plateau at 50ug/ml.comparing with ?-ray irradiation, we observed that PSD-007 could not increase the amount of ssb in cells irradiated with ?-ray and the most of ssb could be rejoined after incubation at 37℃ for 1 hour in the presence of PSD-007. However, DNA ssb induced by photosensitizer and light could not be repaired in post-photorad iated incubation. It is suggested that there exist some differences between the damages induced by photosensitization and by ioning radiation.From our experiment, we believe that DNA damage of cells is an early and critical event in photosensitization, which is different from that induced by y-ray irradiation.

Objective To investigate the inhibition mechanism of tetramethylpyrazine combined with cisplatin on angiogenesis in Lewis lung cancer mice and to observe the mechanism of Arresten on angiogenesis in lung cancer. Methods The model of Lewis lung adenocarcinoma mouse xenograft was established in this work, and 40 mice were randomly divided into 4 groups: 0.9% sodium chloride solution group(NS group), tetramethylpyrazine group(TMP group), cisplatin group(DDP group), tetramethylpyrazine plus cisplatin group(TMP + DDP group), 10 mice in each group.Mice in NS group were given 0.2 mL of 0.9% sodium chloride solution, mice in DDP group were given 0.2 mL of 2 mg.kg-1 of cisplatin, mice in TMP group were given 0.2 mL of 100 mg.kg-1 of tetramethylpyrazine, mice in TMP+DDP group were given 2 mg.kg-1 of cisplatin and 100 mg.kg-1 of tetramethylpyrazine, each 0.1 mL .Tumor size was measured every day to calculate the tumor volume.The mice were sacrificed to stripp the subcutaneous tumor after continuous medication. The expressions of Arresten, integrin α1β1 and VEGF were determinated by immunhistochemistry and Western blotting. Results The tumor growth of NS group was the fastest and TMP+DDP group was the slowest. Compared with NS group, the expression of Arresten in the other three groups was increased( P<0.01) , and the TMP+DDP group exhibited the highest expression;at the same time, integrin α1β1 , VEGF in the other three groups was decreased(P<0.01), and the TMP+DDP group exhibited the lowest expression.The expression of integrinα1β1 and VEGF was negatively related to Arresten, and the expression of integrin α1β1 was positively correlated with VEGF. Conclusion TMP can inhibited the growth of Lewis lung carcinoma and angiogenesis. Moreover, in combination with cisplatin, TMP can also improved the effect of chemotherapy and then the survival state of mice. The mechanism of action, which TMP suppress tumor angiogenesis may be through improving Arresten and inhibiting integrin α1β1 and VEGF. And the action mechanism of Arresten may be implemented by inhibiting the expression of VEGF by incorporation with integrinα1β1 or by itself to inhibit the expression of VEGF.