Biomedical subjects
Publications and source records attributed to Iu D Parfenov.
Results of carcinogenic testing of 4-amino-1,2,4-triazole (AT) in chronic experiments is presented. The testing did not reveal carcinogenic properties of this substance in rats but showed carcinogenicity in F1 mice. AT can be characterized as a substance with limited evidence of carcinogenicity.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Overt dependence of lung tumour development on the values of the dose administered was shown in experiments on inbred white rats under intratracheal administration of various doses of dibenz (a, h) anthracene (DBA); minimal-effect dose and maximal no-effect dose of DBA were established in the experiment. A theoretically calculated allowable dose was used to calculate MAC of the chemical under study for the ambient air 5 ng/m3 was recommended as an average 24-hour maximum allowable concentration of DBA in ambient air.
The results of experiments on the 1,2-dimethylhydrazine (DMH) induction of epithelial renal tumours in CBA male mice are presented. The dose-response study shows a sharp increase (from 5 to 75%) of the epithelial renal tumour incidence in the range of 2, 4 and 8 injections of DMH. Higher doses induce a decrease of the tumour incidence due to the early death caused by other tumours. DMH is shown to be the most powerful renal carcinogen in mice. Serial sacrifice of mice after 5 injections of DMH is a convenient model for the study of renal carcinogenesis in mice. Main histological types of epithelial renal tumours are illustrated.
Maximum allowable 24-hour human intakes of NDMA and NDEA, calculated with the use of a log-normal model, a model of logit-transformations and methods of confidence intervals and probability estimations, are 0.15 micrograms/kg and 0.03 micrograms/kg respectively. Maximum allowable concentrations for NDMA and NDEA in water are 5 micrograms/l and 1 microgram/l respectively.
The administration of estradiol propionate after the discontinuation of 1,2-dimethylhydrazine (DMH) treatment increased the incidence of uterine sarcoma in CBA mice from 32.5 (DMH alone) to 62.5%. The addition of the ascorbic acid (0.3% solution in drinking water) to estradiol propionate was followed by a decrease in the tumor incidence to 35%, i. e. the acid levelled the promoting effect of estradiol propionate almost completely. Sodium ascorbate did not share that effect. Mechanisms underlying the antiestrogenic effect of the ascorbic acid are discussed.
The incidence rate of ovarian and uterine tumours in rats after irradiation by protons with the energy of 645 MeV, 9 GeV and He2+ has been studied. The tumour rate is shown to increase with the radiation dose. The character of the dose-response for tumours of two sites is different. A relative risk of ovarian tumour incidence after He2+ exposure is twice as high as after other types of radiation.
The study was concerned with the influence of single dose of estradiol dipropionate on its promoting effect on 1,2-dimethylhydrazine-induced tumors in female CBA/CaLac mice. Estradiol dipropionate given within 19 weeks did not affect carcinogenesis whereas 39-week treatment stimulated uterine sarcoma development irrespective of single dose and schedule of administration.
The role of dose and time factors in intensification of the carcinogenic effect is studied on the model of skin carcinogenesis in (CBA x C57Bl)F1 female mice under application of BP. The total dose is not a single parameter determining the carcinogenic effect. The single dose interval between the actions and their number are of essential importance under definite conditions. The total time (T) of the carcinogen action is a significant factor. The total and single doses and the number of carcinogen applications to the mouse skin being similar, the effect is the stronger, the longer is T, i.e. the longer is the interval between certain applications of the carcinogen.
The study used 8 groups of 8-10 week-old male hamsters. Beeswax pellets containing 5 mg of 20-methylcholanthrene (group 4) or 2 mg (group 5) were injected into the gallbladder. In group 6, the latter treatment was supplemented with castration and subcutaneous injection of 40 micrograms of estradiol dipropionate (EP) once a week. Other experimental exposures included: sham operation (group 2), beeswax pellet injection into the gallbladder (group 3), beeswax pellet injection + castration + EP (group 7) and castration + EP (group 8) with the animals is group 1 being in control. The gallbladder tumor development frequency in groups 4, 5 and 6 was 58.3; 39.3 and 77.8%, respectively. The difference between the data on group 5 and 6 proved significant. The study on cumulative likelihood of tumor development showed a significant increase in tumor frequency in group 6 as compared with group 4 and 5. A strong stimulating effect of castration and EP treatment on tumorigenesis in the gallbladder was demonstrated.
Explore the source record for details and available documents.
The carcinogenic effects of coal tar and benzo(a)pyrene were compared. The agents were applied to murine skin, with coal tar dose being adjusted for benzo(a)pyrene. The carcinogenic effect of coal tar appeared higher than that of benzo(a)pyrene, the relative carcinogenic risk of the former being 3.2 times that of the latter. The coefficient of relative carcinogenic risk of coal tar calculated on the basis of TD56 regression coefficients for dose-effect relationship and mean latent period ratios was averagely 1.5.
The (CBA x C57Bl)F1 female mice were treated with weekly injections of 1,2-dimethylhydrazine (DMH) at a dose rate of 4.15 mg/kg of body weight during different time periods. Relations between the incidence of organ specified particular tumours depend on the total DMH dose. Incidence of haemoblastoses decreases with an increase in the DMH dose. Dose relationships of the tumour incidence are analyzed statistically by the method with intercurrent mortality corrections and carcinogen effect expressed by relations of the observed and expected numbers.
Explore the source record for details and available documents.
Uterine sarcomas in (CBA X C57B1)F1 mice receiving 1,2-dimethylhydrazine (DMH) developed in 20% of animals. Concomitant administration of estradiol-dipropionate (EP) in doses of 2, 10 and 30 micrograms/mouse significantly increased tumour incidence up to 46.9, 62.5, and 50%, respectively, and shortened their latency: 42.3 weeks in a group receiving DMH alone and 36.7, 38.4 and 30.5 weeks in groups receiving DMH plus 2, 10 or 30 micrograms EP, respectively.
A method of permissible dose assessment for chemical carcinogens is presented. The method is based on regulatory implications in terms of the tumour occurrence probability and on the used non-threshold concept. The cumulative log-normal distribution function is used as a mathematical model of the dose-effect. Equation parameters are estimated by the least square method.
The paper discusses the advantages offered by the statistical evaluation of experimental carcinogenic effect with due regard to mortality from concomitant pathology. The method used complex tables of contingents and analysis was carried out separately in 3 groups of tumors--independent of mortality, fatal and incidental ones. The method was compared with standard procedures which do not take care of the said mortality rate (table of contingents 2 X 2 and precise procedure of Fisher). The data on development of 1,2-dimethylhydrazine-induced tumors of the skin, uterus and ovaries in 5 strains of mice were used in the study.