Biomedical subjects

M H Kuczuk

Publications and source records attributed to M H Kuczuk.

5 recordsLinked to original sources

PubMed1984

Potentiation of acetazolamide induced ectrodactyly in SWV and C57BL/6J mice by cadmium sulfate.

CdSO4 and acetazolamide each induce postaxial ectrodactyly in rodents when administered at a critical time in forelimb development. C57BL/6J mice are extremely sensitive to the teratogenic action of both agents, whereas SWV mice are relatively resistant. Additionally, both of these agents can inhibit carbonic anhydrase. In the present study administration of CdSO4 and acetazolamide in combination to either strain of mice potentiates the incidence of forelimb ectrodactyly. These results, in combination with the aforementioned similarities of teratogenesis, suggest a common mechanism of teratogenesis.

Abnormalities, Drug-Induced↗

PubMed1984

Comparative inhalation teratogenicity of four glycol ether solvents and an amino derivative in rats.

Previous research demonstrated the inhalation teratogenicity of the solvent 2-ethoxyethanol in rats and rabbits. As this is one of a class of widely used industrial solvents, we investigated the teratogenicity of five structurally related compounds. Each chemical was vaporized and administered to approximately 15 pregnant rats in one to three concentrations for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20. Fetuses were individually weighed, and two-thirds of them were fixed in Bouin's solution and examined for soft-tissue anomalies. The other one-third were fixed in alcohol, stained with Alizarin Red and examined for skeletal defects. Data were analyzed on a litter basis; three solvents were compared with a pooled group (N = 34) of sham-exposed controls, and the remaining two were compared with a group of 15 controls. At concentrations which were apparently not maternally toxic, 2-methoxyethanol was highly embryotoxic, producing complete resorptions at 200 ppm; increased resorptions, reduced fetal weights and skeletal and cardiovascular defects occurred at both 100 and 50 ppm. 2-ethoxyethyl acetate at 600 ppm induced complete resorption of litters; 390 ppm reduced fetal weights and induced skeletal and cardiovascular defects, but only a single defect was observed at 130 ppm. 2-Butoxyethanol evidenced slight maternal toxicity at 200 ppm but produced no increase in congenital defects at that concentration. Neither 2-(2-ethoxyethoxy)ethanol (100 ppm) nor 2-methylaminoethanol (150 ppm) was maternally toxic or embryotoxic. In summary, shorter alkyl chained glycol ethers produced greater embryotoxicity than those having longer chains, and the ester produced effects equivalent to the ether, both patterns predictable from the biochemical literature.

Abnormalities, Drug-Induced↗

PubMed1982

Teratogenicity of 2-ethoxyethanol by dermal application.

Undiluted 2-ethoxyethanol or water (control) was applied to the skin of pregnant Sprague-Dawley rats on days 7--16 of gestation (sperm = day 1). Applications were made 4 times daily in volumes of 0.25 or 0.50 ml 2-ethoxyethanol. Females exhibited ataxia following treatment of the high-dose group, and weight gain was significantly (p less than u. 0.001) reduced in the last half of gestation. Litters were collected by caesarian section on day 21 of gestation, and fetuses were examined for external defects. Half of the fetuses were cleared and stained in alizarin red S for skeletal examinations, and half were examined for visceral defects by the Wilson technique. Intrauterine death was 100% in the high-dose group. In the lower dosage group, there was a significant increase in the number of pregnant females with 100% dead implants (p less than 0.001), a significant reduction in the number of live fetuses per litter (p less than 0.001), a significant reduction in fetal body weight (p less than 0.001), and a significant increase in the incidence of skeletal variations (p less than 0.05) and cardiovascular malformations (p less than 0.05).

Abnormalities, Drug-Induced↗

PubMed1978

Effects in mice of simultaneous prenatal exposure to ochratoxin A and T-2 toxin.

Aspergillus ochraceus and Fusarium tricinctum are food contaminating molds whose toxic metabolites, ochratoxin A and T-2 toxin, are known mammalian teratogens. In order to determine the possible effects of simultaneous exposure to such environmental agents, ochratoxin A (2 or 4 mg/kg) and T-2 toxin (0.5 mg/kg) were injected ip, either together or individually, in CD-1 mice on gestation days 8 or 10. Ochratoxin induced craniofacial malformations when given alone on day 8, but not on day 10. T-2 toxin induced tail and limb anomalies particularly when given on day 10. When the two toxins were given together on day 10, ochratoxin exacerbated the incidence of T-2 induced gross malformations. An increase in fetocidal effects was also noted in groups treated at the high dose combination on either day, and effects on fetal growth of the high dose combination given on day 10 were greater than those of the other treatments. Few skeletal or visceral malformations were noted. These results indicated that two teratogens with presumably differing mechanisms of teratogenesis may have additive effects when administered concurrently to the same animal. Such results could be due to generalized toxic effects on the fetus or to more specific mechanisms, but further information is needed to differentiate between the two possibilities.

Abnormalities, Drug-Induced↗

PubMed1978

Evaluation of the mutagenic potential of mycotoxins using Salmonella typhimurium and Saccharomyces cerevisiae.

The mutagenic effects of fiteen mycotoxins on Salmonella typhimurium strains TA1535, TA1537 and TA1538 and Saccharomyces cerevisiae strain D-3 were tested. Only aflatoxin B1 and sterigmatocystin were mutagenic. Both were active against S. typhimurium strain TA1538 and S. cerevisiae strain D-3; however, both required activation by the hepatic S-9 enzyme preparation. A positive correlation between the other mycotoxins reported to be carcinogenic and the two in vitro test systems employed was not demonstrated in our hands.

Aflatoxins↗