ABSTRACT
7-Methylguanine (7-MG) competitively inhibits the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and RNA-modifying enzyme tRNA-guanine transglycosylase (TGT) and represents a potential anticancer drug candidate. Furthermore, as a natural compound, it could escape the serious side effects characteristic for approved synthetic PARP inhibitors. Here we present a comprehensive study of toxicological and carcinogenic properties of 7-MG. It was demonstrated that 7-MG does not induce mutations or structural chromosomal abnormalities, and has no blastomogenic activity. A treatment regimen with 7-MG has been established in mice (50 mg/kg per os, 3 times per week), exerting no adverse effects or changes in morphology. Preliminary data on the 7-MG anticancer activity obtained on transplantable tumor models support our conclusions that 7-MG can become a promising new component of chemotherapy.
ABSTRACT
OBJECTIVE: Study of embryotoxicity, teratogenicity and reproductive toxicity of the new drug Lipophtalocyan in rats. MATERIAL AND METHODS: Studies were conducted on 210 non-inbred female rats and 105 non-inbred male rats. The drug was administered daily via i. v. injection for 48 days (males) and for 15 days (females) in 2 total doses corresponding to the therapeutic dose (TD) for mice when converted to rats and 10 TD. RESULTS AND CONCLUSION: When mating with intact female rats, no changes in sexual behavior were observed, but the index of the ability to fertilize and conceive decreased when compared to the values of the control group by 35-40% (TD index=60%) and by 75-80% (10 TD index=20%). The index of the ability to fertilize and conceive differed from the values of the control group by 90% (TD index=5%) and by 15% (10 TD index=80%). There were no differences in the indicator of embryotoxicity and teratogenicity in intact and drug-treated female rats, compared with the control group. Lipophtalocyan has a negative effect on the male and female reproductive function in rats and has an embryotoxic effect according to the index of the ability to fertilize and conceive, as well as the indices of preimplantation and post-implantation fetal death. The drug does not have a teratogenic effect, neither it affects the physical development of offspring or the rate of maturation of sensory-motor reflexes during feeding.
