Study On Genotoxic Effect Of DNA,RNA Damage Induced By Formaldehyde And Benzene

Objects: Formaldehyde (FA) and benzene (BZ) are volatile organic compounds and important indoor air pollutants caused by decoration and fitment , which are used as in decoration materials. There are the characteristics of high concentration in indoor air and serious biological toxicity to bio-body. However, combined toxicity effect and mechanisms induced by FA and benzene are poorly published. The aim of this study is to explore alone /combined genotoxic effect and mechanisms of DNA> RNA damage induced by FA and benzene and provide experimental data to choice early biomarkers that reflect damage of body induced by FA and benzene.Methods: In the present study, the Chinese hamster lung fibroblast cell(V79) was used to explore the cytotoxicity of V79 cells induced by FA in vitro , and consult literature offering the bases for dosage in the latter parts; DNA, RNA damage induced by different concentration FA and Hydroquinone were detected with Alkli single cell gel electrophoresis (SCGE) and the assay of radioactive compounds (³H-thymidine and "C-Uridine) incorporation in V79 cells. To provide new information for the study of alone /combined genotoxic effect and mechanisms induced by FA and benzene, DNA, RNA damage of peripheral blood white cells and lymphocytes induced by different concentration FA and benzene were detected with SCGE and the assay of radioactive compounds (³H-thymidine and ¹⁴14C-Uridine) incorporation in mice in vivo.Results: Formaldehyde could cause DNA cross-links of V79 Chinese hamster cells, except for the 75μmol/L dose, the DNA cross-links were increased with concentration of formaldehyde and expose time in vitro studies.The ³H-thymidine and ¹⁴C-Uridine incorporation disintegrations per minute (dpm) of DNA and RNA in FA-treated V79 Chinese hamster cells was significantly lower than that of the control group, except for the 75μmol/L dose at 1h and2h. The incorporation (dpm) of 75, 150. 300, 600 \mol/l FA-treated at 4h was significantly lower than that of ones at lh and 2h(P<0. 01).Hydroquinone could cause significant DNA damage at the all groups concentrations tested, the rate of cells with tail was 69%-, the mean values of tail length was 42. 20 + 3. 18fam in low dose group(150^mol/L)and the rate of cells with tail was 91%, the mean values of tail length was 47. 05±4. 31(j.m in high dose group(2400|amol/L), but no clear dose-dependent response.After i. p. administration of alone /combined FA and benzene at different dose, except for the lOOmg/kg dose of benzene, the !H^thymidine and MC-Uridine incorporation dpm of DNA and RNA induced by alone/combined formaldehyde and benzene was significantly lower than that of the control group within the doses given in vivo, and significant decrease the percentage of 'H-thymidine and l4C-Uridine incorporation dpm of DNA and RNA induced by combined FA and benzene compared with that of formaldehyde, benzene, respectively (fK0.05).Conclusion: FA can cause the cytotoxicity and DNA cross-links in V79 cells. DNA and RNA synthesis were significantly affected by FA in Chinese hamster cells, and a dose and time-response relationship was shown in vitro assay. DNA and RNA synthesis of lymphocytes in mice were significantly affected by FA within the doses given in vivo, and a dose-response relationship was shown. DNA cross-links may be a biomarker that detected damage of bio-body induced by FA.HQ can cause DNA damage of V79 cells. Benzene can cause DNA damage of peripheral blood cells. DNA and RNA synthesis of lymphocytes in mice were significantly affected after i. p. administration of benzene at different dose in vivo, and a dose-response relationship was show within the doses given.DNA breakage of V79 cells was found at low concentration of FA(75(amol/L) mixed with HQ(150famol/L), and at high concentration of FA mixed with HQ , DNA cross-links of V79 cells were induced in vitro. After i. p. administration of FA and benzene at different dose , FA and benzene could significantly affect DNA and RNA synthesis of lymphocytes in mice compared with those of formaldehyde, benzene, respectively in vivo, which suggest that there is a combined effect of FA and benzene on bio-body.In a conclusion, the experimental results suggested that FA and benzenecould lead to multiple organs toxicity and genotoxicity in vivo and in vitro, and induce a combined genotoxic effect of DNA, RNA damage.It can also be concluded that SCGE is a sensitive, rapid and convenient way to detect DNA damage induced by the environmental toxins, and UV is used as standard DNA breaking agents, and the DNA cross-links induced by the environmental toxins can be rapidly, conveniently detected with SCGE.