METHOD FOR ASSESSING TOTAL VALUE OF GENOTOXIC EFFECTS OF DRUGS AND ENVIRONMENTAL FACTORS Russian patent published in 2024 - IPC G01N33/48 G16B40/00 

FIELD: biology; medicine.

SUBSTANCE: described is a method for assessing the total value of genotoxic effects of a potential genotoxicant. Method involves analysis by the method of an alkaline version of DNA-comets. Study is carried out with registration of DNA damage values in two time points of exposure to a genotoxicant, in samples of embryos and/or placenta of 10 rats, 5 rats in each time point t1 and t2, determining the % DNA comet in separate cells of the samples of embryos and placentas. Further, the distribution and ratio of cells with different degree of DNA damage are determined on the scale of the cell-tissue level of embryos and placentas in each time point of exposure t1 and t2. Cells in which the % DNA value in the comet tail is up to 10% are taken as the norm with a physiologically permissible level of DNA unwinding and/or spontaneously determined breaks. Cells with % DNA in comet tail is 10-50% are established as an indicator of genotoxic effect. Cells with % DNA in comet tail is more than 50% are considered to be apoptotic. Further, the total AUC_t2-t1 is determined, which describes the relationship % DNA-comets – time. If determining the total value of genotoxic effects, calculating the average value of the % DNA in the comet tail up to 50%, measured in separate samples through t1 and t2 hours after treatment with the genotoxicant, further, the parameter AUC_t2-t1 is determined by the formula of the area of trapeziums in the modification, then, based on a sample of all embryos and/or placentas from 10 rats. If the total index of apoptotic damage describing the dependence of apoptotic comets – time is determined, then the index of apoptotic comets is calculated, measured in separate samples through t1 and t2 hours after treatment with the genotoxicant. Further, the average value is determined for a sample of embryos and placentas from 10 rats, wherein the parameter AUC_t2-t1 is determined using an algorithm similar to that described for the relationship % DNA-comets – time. Also described is the use of the method according to cl. 1 in biological and medical research.

EFFECT: invention can be used in experimental pharmacology and targeted preclinical research programs for prediction of genotoxic risk of congenital malformations and safety of medical use of drugs.

2 cl, 2 dwg, 6 tbl