ABSTRACT
The anticlastogenic effect of tannic acid was studied in vivo in the mouse micronucleus test. The frequencies of micronuclei induced by mitomycin C, ethyl nitrosourea (ENU) or 4-nitroquinoline 1-oxide in mouse bone marrow cells were decreased by the oral administration of tannic acid 6 h before the mutagen injection. The observed suppressing effect was not a reflection of a delay in the formation of micronuclei by the cytotoxic effect of tannic acid. The antimutagenic effect of tannic acid was also investigated in vivo in the mouse spot test using male PW and female C57BL/10 mice. Tannic acid was given orally to pregnant females 6 h before the intraperitoneal injection of ENU on the 10th day of pregnancy. The frequency of pups with recessive color spots induced by ENU was decreased by the administration of tannic acid. The observed decrease was not due to toxic effects on the embryo. These results indicate that tannic acid acts as an anticlastogen and antimutagen in vivo.
Subject(s)
Hydrolyzable Tannins/toxicity , Tannins/toxicity , 4-Nitroquinoline-1-oxide/toxicity , Animals , Ethylnitrosourea/toxicity , Male , Mice , Micronuclei, Chromosome-Defective , Mitomycins/toxicity , Pigmentation/geneticsABSTRACT
The antimutagenic effects of vanillin, anisaldehyde, cinnamaldehyde and coumarin were investigated in cultured Chinese hamster V79 cells in vitro. The frequencies of 6-TG-resistant mutations induced by UV or X-rays were decreased by treatment with each compound during the expression time. These decreases were not due to cytotoxic effects on cellular growth or killing effects on damaged cells. The antimutagenic effect of vanillin was also investigated in vivo in the mouse spot test using male PW and female C57BL/10 mice. Female mice were injected intraperitoneally with ethylnitrosourea (ENU) on the 10th day of pregnancy and received 3 successive oral administrations of vanillin. Administration of vanillin decreased the ENU-induced frequency of recessive carrier pups. These results indicate that vanillin acts as an antimutagen in mammalian cells both in vitro and in vivo.
Subject(s)
Benzaldehydes/pharmacology , Mutation , Thioguanine/pharmacology , Acrolein/analogs & derivatives , Acrolein/pharmacology , Animals , Cells, Cultured , Coumarins/pharmacology , Drug Resistance/genetics , Ethylnitrosourea/metabolism , Ethylnitrosourea/toxicity , Female , Male , Mice , Mice, Inbred C57BL , Mutagenicity Tests , Pregnancy , Ultraviolet Rays , X-RaysABSTRACT
The spot test with 1,2-dibromo-3-chloropropane (DBCP) was carried out using male PW and female C57BL/6 mice. DBCP induced recessive colour spots in offspring with a significantly high frequency of 2.9%, showing that this chemical is mutagenic for somatic cells of mice in vivo.
Subject(s)
Genes, Recessive/drug effects , Insecticides/toxicity , Mutation , Propane/analogs & derivatives , Animals , Crosses, Genetic , Ethylnitrosourea/toxicity , Female , Hair Color/drug effects , Male , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Mutagenicity Tests/methods , Pregnancy , Propane/toxicityABSTRACT
Mono(2-ethylhexyl) phthalate (MEHP), one of the main metabolites of di(2-ethylhexyl) phthalate (DEHP), exerted embryo/fetotoxic effects similar to those of DEHP at lower doses. Oral administration of MEHP (1 mL/kg) to the mice of 8 days gestation resulted in less than 32% of live fetuses, all of which were deformed. When DEHP (10 mL/kg) was given to the pregnant mice of 8 days gestation, approximately 0.03% and 0.003% of the administered dose was found in fetuses as DEHP and MEHP, respectively, after 12 hr. The presence of the MEHP in fetuses is probably due to the transplacental crossing of the MEHP formed in the maternal body, since the fetuses of mice up to day 9 of pregnancy showed no hydrolytic activity of DEHP to MEHP. Crossing of MEHP through the placenta was proven by an experiment in which MEHP was administered in pregnant mice. A single injection of MEHP (25 or 50 mg/kg), but not DEHP (500 mg/kg) into pregnant mice, induced a significantly high incidence of somatic mutations in the coat hair of offspring of mice (KYG, female X PW, male; C57BL/6Crj, female X PW, male). All these data suggest that MEHP could be responsible for the embryotoxic/fetotoxic effects observed with DEHP.
Subject(s)
Abnormalities, Drug-Induced/etiology , Diethylhexyl Phthalate/toxicity , Phthalic Acids/toxicity , Abnormalities, Drug-Induced/metabolism , Administration, Oral , Animals , Diethylhexyl Phthalate/analogs & derivatives , Diethylhexyl Phthalate/metabolism , Female , Fetal Death/chemically induced , Genes, Recessive , Hydrolysis , Mice , Mutation/drug effects , Pregnancy , Tissue DistributionABSTRACT
The effect of the Slt mutant gene on the production of melanocytes, tissue mast cells, and erythrocytes was compared with the effect of the Sl and Sld mutant genes on the same genetic background [(WB X C57BL/6)F1 mice]. Although the rank order of cell numbers was similar in these three types of cells (i.e., +/+ greater than Slt/Slt greater than Sld/Slt greater than Sl/Slt greater than Sl/Sld), the difference in the melanocytes was largest, and the difference in the erythrocytes was smallest. Since male Slt/Slt mice (on both WB and C57BL/6 backgrounds) were fertile, such mice were useful for efficient production of moderately mast-cell-deficient Sl/Slt and Sld/Slt mice.
Subject(s)
Mast Cells/cytology , Mutation , Alleles , Animals , Erythrocytes/cytology , Female , Hematopoiesis , Male , Melanocytes/cytology , Mice , Mice, Mutant Strains , Skin/cytologyABSTRACT
The embryonic/fetotoxic effects of DEHP on pregnant mice (ddY-Slc female x CBA male) were studied. DEHP was administered orally in dosages of 0.05 ml/kg to 30.0 mg/kg on day 6, 7, 8, 9 or 10 of gestation. A single administration of DEHP over 0.1 ml/kg (1/300 of LD50) on day 7 of gestation decreased the numbers and the body weight of living fetuses, whereas no significant changes in the numbers of living fetuses (with no gross and skeletal abnormalities) were observed compared with those of the control group, when 0.05 ml/kg (1/600 of LD50) of DEHP was administered. The fetotoxicity (fetal death) was dose dependent. The LD50 and the nonfetolethal maximum dosage of DEHP in its single, oral administration was 592 mg/kg and 64 mg/kg, respectively. The latter value is much higher than an estimated DEHP intake from commercial foodstuffs in men, which is approximately 0.03 mg/kg/day.
Subject(s)
Bone and Bones/abnormalities , Diethylhexyl Phthalate/toxicity , Fetal Death/chemically induced , Phthalic Acids/toxicity , Teratogens , Animals , Body Weight/drug effects , Dose-Response Relationship, Drug , Female , Maternal-Fetal Exchange , Mice , PregnancyABSTRACT
Spot tests with various alkylnitrosoureas were carried out using the newly established PW strain of male and female C57BL/6 mice. Chemicals tested were N-methyl-N-nitrosourea (MNU), N-ethyl-N-nitrosourea (ENU), N-propyl-N-nitrosourea (PNU) and N-butyl-N-nitrosourea (BNU). Although MNU had a severe teratogenic effect, no clearly positive color spot was obtained, while apparent induction of their color spots was observed with ENU, PNU and BNU. The frequency of appearance of these color spots was dose-dependent. In F1 males from the treated group, the weight of the testes was significantly lower in mice about 30 days old. It is suggested that these chemicals may have mutagenic effects on both developing somatic and germ cells of mice.
Subject(s)
Nitrosourea Compounds/pharmacology , Animals , Ethylnitrosourea/pharmacology , Female , Male , Methylnitrosourea/pharmacology , Mice , Mice, Inbred Strains , Mutagenicity Tests , Mutagens/pharmacology , Reproduction/drug effects , Structure-Activity Relationship , TeratogensABSTRACT
The specific-locus test was performed with N-ethyl-N-nitrosourea (ENU) on spermatogonia of mice by using visible loci and a hemoglobin beta-chain (Hbb) locus. Male wild-type (C3Hf/He) mice were injected intraperitoneally with ENU. 8 weeks after injection, these males were mated with tester strain females (PW). 9 visible mutants and the 1 Hbb locus mutant were obtained. This Hbb locus mutation was heritable and viable under homozygous conditions, suggesting that it might have resulted from events at the molecular level.
