Analysis of the Phenotype and the Restriction Enzyme Mapping Level of Mutations Induced by the New Mutagen Glycidyl Methacrylate

Glycidyl methaerylate (GMA) is a recently recognized chemical mutagen. In order to explore the mutagenicity and mutagenic process of GMA, plasmid pBR322 was used for in vitro binding, mutant screening, and restriction enzyme mapping. The binding between GMA and DNA in vitro has been verified by means of a spectrophotometric method. When pBR322 and GMAbound pBR322 were used to transform Eschenchia coli HB101, the following results were obtained: (1) The transformation efficiency of GMA-bound pBR322 was much lower than that of pBR322 alone. (2) GMA-bound pBR322 induced phenotype changes in competent cells (i.e., tetracycline-resistance inactivation or ampicillin-resistance inactivation). There were two mutants of pBR322, Ap~RTc~S and Ap~STc~R, in the transformants and a deductive mutant Ap~STc~S in the nontranstormants. (3) All of the selected mutants were stable and heritable. (4) When restriction enzyme maps were used to analyze the mutant Ap~RTc~S, four of seven maps were changed. some sites were shifted to other resistant gene regions, for example, sites of Bgll, EcoRl, Ilindlll. Hinclll, etc., and there was a new recognition site for Hindi (252). We did not observe any DNA fragment insertion or deletion on any maps. Our results suggest that when GMA is covalently linked to the plasmid DNA, it gives rise to a premutagenic lesion of DNA that is converted in vivo into a point mutation. (C)1990 Academic Press, Inc.

Remediation of Hepatotoxic Effect of Tamoxifen with Ginger in Rat Model

Background:Tamoxifen is a non-steroidal oestrogen receptor modulator.It has strong anti-estrogenic activity on oestrogen receptor 2 in the breast tissue.It is the treatment of choice in breast cancer cases following surgery and radiotherapy,it is the most potent weapon against breast cancer.All stages of hormone-dependent breast cancer are currently treated with tamoxifen.Long-term tamoxifen therapy may cause hepatotoxicity which would perclude the use of tamoxifen.Hence this study was done to determine whether ginger has a role in protecting liver toxicity caused by tamoxifen.Methods:Twenty female albino rats(SD)were divided into 4 groups.Each group formed of five rats:Group I:Serves as control group received normal rodent diet and water,GroupⅡ:Received ginger powder(200 mg/kg)dissolved in normal saline,orally daily for 6 weeks,GroupⅢ:received TAM at a dose of 20 mg/kg daily for 6 weeks orally GroupⅣ:Received TAM(20 mg/kg)then after 2 hrs they are orally given Ginger powder(200 mg/kg)daily for 6 weeks.Results:Tamoxifen 20 mg/kg/day caused hepatotoxicity in rats.When ginger is added to tamoxifen there is no development of hepatotoxic features like:marked sinusoidal congestion in the lobules and lab parameters showed decrease in serum AST and ALT levels when compared to tamoxifen group levels.Conclusion:Ginger supplementation would reduce the incidence of hepatotoxicity&related adverse drug reactions among breast cancer patient on therapy.