| Objective. The governments all over the world have paid much attention to the examination of new drug and set up a series of laws to standardize the examination of new drug. Among them, it's of great importance to value the toxicity of new drug. In order to guarantee the safety of new drug using in clinical, the letterpress evaluate the security of H98 from genotoxicity toxicity and reproductive toxicity . Genotoxicity toxicity test are composed of Ames test, chromosomal aberration of cultivated mammal cell test and the micronucleus test. On the basis of finished mutation research, Genotoxicity toxicity tests such as sister-chromatid exchange and the cytokinesis-block micronucleus assay were used to assess the induced mutation of H98. In this study, the reproductive toxicity test was used to value the effects of H98 on capability of pregnancy, genitalia and their offspring of female and male animals after their sperm contacted H98.Methods 1 Genotoxicity toxicity test: such as sister-chromatid exchange, the cytokinesis-block micronucleus assay and mutation rate at the hprt locus were used. CHL cells were planted in 25ml bottle at approximately 5?05 cells per bottle and incubated at tissue-culture flasks at 37癈 in a humidified atmosphere containing 5% CO2.After 18h ,the treatment drug of different concentrations were plused in culture-bottles. In SCE experiment, add Brdu to marking chromosome, select the second cycle segmentation phase to count the frequency of SCE. In cytokinesis-block micronucleus assay experiment, add Cyt-B to suppress cytoplasm division ,it presented double- nucleus cell, every marking count 3000 double-nucleus cells and their micronucleus rate (%o); hprt gene spot in mutation assay, use mutation cell amount contain 6-TG sample in 1000 cells (double-nucleus cells or multi-nucleus cells) divided by the mutation cell amount not contain 6-TG sample in 1000 cells, it was the mutation rate at the hprt locus (10-3) , 2 Reproductive toxicity test: The male rats ranging in weight from 25g to 35g were divided into 4 groups randomly. Each group comprised 20 rats. Three groups ofdosages (12.5, 50.0, 200.0mg.kg ' respectively) of H98 were administered by injected into gaster for 9 weeks. The same volume of 0.2%sodium carboxymethyl cellulose was administered to the control groups. The female rats ranging in weight from 28g to 35g were divided into 4 groups randomly. Each group comprised 35 rats. H98 was administered before copula. On the 14 and 18 day of their pregnancy, the female rats were anatomized. The female rats have the same dosages and way as male rats have.Result 1 Genotoxicity toxicity test: Compared with control group, H98 had no significant effects on sister-chromatid exchange, the cytokinesis-block micronucleus assay and mutation rate at the hprt locus of the groups administered (P>0.05). 2 Reproductive toxicity test: (1)Compared with control group, H98 had no significant effects on birth rate of the male group administered (p>0.05) and on the number of sperm, live sperm ratio and malformative sperm ratio of the male group administered. Testes didn't show aberration by pathological assay. (2) Compared with control group, H98 had no significant effects on pregnancy rate of the female group administered (p>0.05). It was proven by anatomy that pregnancy rats administered with 200.0mg.kg"1 had much higher lost rate of embryo than the control group. (3) H98 had no significant effects on development of the offspring rats.Conclusion 1 Genotoxicity toxicity test : (1)H98 had no significant effects on frequency of sister-chromatid exchange . (2)the cytokinesis-block micronucleus assay and mutation rate at the hprt locus are negative (3)It is shown that H98 had no significant effects on the capability of pregnancy and genitalia of rats. H98 over 200.0mg.kg"1 shows embryo toxicity. |
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