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Biomedical subjects

A A Frank

Publications and source records attributed to A A Frank.

10 recordsLinked to original sources
PubMed1992

Ellagic acid protects rat embryos in culture from the embryotoxic effects of N-methyl-N-nitrosourea.

Ellagic acid is a naturally occurring plant phenol that has demonstrated anticarcinogenic and antimutagenic activity in several test systems. Given the common proposed etiopathogenic processes of mutagenesis, carcinogenesis, and teratogenesis induced by genotoxic chemicals, the present study was initiated to determine whether ellagic acid would protect rat embryos in culture from the teratogenic effects of N-methyl-N-nitrosourea (MNU). Ellagic acid alone (as used in these experiments; 50 microM in DMSO) was not embryotoxic. Ellagic acid (50 microM) significantly (P less than 0.01) prevented MNU (75 microM)-induced effects including mortality (absence of heart beat), abnormal formation of the cephalic neural tube derivatives, and delayed differentiation as assessed by a morphological scoring system. These embryoprotective effects were dose responsive. Sequential treatment of embryos with ellagic acid followed by MNU in fresh media also was embryoprotective with no diminution of effect. The site at which ellagic acid interrupts the critical teratogenic events induced by MNU is apparently within the embryo and/or placenta. This model of chemical embryoprotection may be useful in determining the role of cell death and/or mutation in the teratogenic mechanism of action of methylating agents.

Abnormalities, Drug-Induced↗
PubMed1992

Flow cytometric analysis of thymic lymphosarcoma induced by N-methyl-N-nitrosourea in C57B1/6J mice.

N-Methyl-N-nitrosourea (MNU) induces thymic lymphosarcoma in numerous mouse strains. We determined the neoplastic phenotype induced by MNU in 20 C57B1/6J mice. Eleven neoplasms were composed of cells that were CD4-CD8+, four neoplasms were composed of cells that were CD4+CD8+, two neoplasms were mixtures of CD4+CD8+ and CD4-CD8+ cells, and three neoplasms were made up of cells that expressed neither CD4 nor CD8. Expanded populations of CD4+CD8- cells were observed within individual neoplasms. Of 10 neoplasms that were further classified, all were composed of cells that were J11d+, indicating immaturity. CD3 expression was generally negative, while IL2R expression was variable in these neoplasms. These data from C57B1/6J mice, a strain with a low incidence of spontaneous (viral-associated) thymic lymphosarcoma, indicate that a continuous spectrum of immature phenotypes are produced by MNU. The finding that each immature cell population can be expanded in this model system differs from previous reports. Our data do confirm the general finding in AKR mice, a strain with a high incidence of spontaneous thymic lymphosarcoma, that cells with immature phenotypes, particularly CD4-CD8+J11d+, make up MNU-induced thymic lymphosarcomas.

Animals↗
PubMed1992

Renal transplacental carcinogenicity of 3,3-dimethyl-1-phenyltriazene in rats: relationship of renal mesenchymal tumor to congenital mesoblastic nephroma and intralobar nephrogenic rests.

Exposure of rat embryos to 3,3-dimethyl-1-phenyltriazene (DMPT) results in numerous malformations, but the urogenital system is not affected. In contrast, exposure of rat fetuses to DMPT has been reported to result in renal neoplasms, which were not further classified. To better understand this discrepancy in organotropism of the teratogenic and transplacental carcinogenic processes, the present study was undertaken to characterize the neoplasms induced in rat fetuses exposed to DMPT in utero. Renal neoplasms and persistent mesenchyme were observed in 19.2 and 11.5%, respectively, of the offspring of rats treated with 1 mg DMPT/kg body weight intraperitoneally on gestation days 16, 18, and 20. The majority of these renal lesions were observed in females. The renal neoplasms were mixtures of various types of mesenchymal tissue derivatives including smooth muscle and fibrous connective tissue. These neoplasms would be classified as renal mesenchymal tumors in rats. Brain neoplasms (numerous types), compound odontomas, and micrognathism were observed predominantly in male offspring from the same group. This treatment also resulted in decreased body weights, increased incidence of sudden loss of body weight, tremors and ataxia, and hypoplastic testes. Exposure to single intraperitoneal doses of DMPT on gestation day 20 did not produce a classic dose-response pattern: Minimal effects were observed with 10 mg DMPT/kg (occasional renal mesenchymal tumors and brain neoplasms), marked effects were observed with 30 mg DMPT/kg (lower incidence rate of most of the alterations observed with 1 mg/kg on gestation days 16, 18, and 20), and no effects were observed with 60 mg DMPT/kg. DMPT administered intraperitoneally at 1 mg/kg body weight on gestation days 16, 18, and 20 is an animal model of transplacental chemically induced renal neoplasms, which provide lesions with similarities to both intralobar nephrogenic rests and congenital mesoblastic nephroma of humans. Why the kidney is a carcinogenic target and not a teratogenic target remains unknown.

Animals↗
PubMed1992

Toxic epidermal necrolysis associated with flea dips.

A 5-y-old intact female Himalayan cat was dipped with an organophosphate-based compound for flea infestation. The animal subsequently died of organophosphate intoxication. Skin lesions present at necropsy were diagnosed microscopically as toxic epidermal necrolysis. A 5-y-old spayed female Corgi dog was dipped with a d-limonene-based compound for flea infestation. The dog subsequently developed a bullous skin disorder which rapidly progressed to severe coalescing necrotizing dermatitis with large areas of skin sloughing. The dog was treated for a tentative diagnosis of toxic epidermal necrolysis with a short course of corticosteroids and extensive supportive care and recovered completely. Flea dip preparations have the potential to induce severe immune-mediated dermatopathies such as toxic epidermal necrolysis.

Animals↗
PubMed1991

Teratogenicity of 3,3-dimethyl-1-phenyltriazene: distribution in rats and rat embryos.

3,3-Dimethyl-1-phenyltriazene (DMPT) is a methylating agent which is carcinogenic, teratogenic and mutagenic which, in the rat, provides a reproducible animal model with which to study the basis of chemically-induced micrognathism. The basis of teratogenic organotropism of DMPT and other methylating teratogens is unknown. The present study was undertaken to determine if limited chemical distribution within the embryo was responsible for the organotropism of DMPT. Whole-embryo autoradiographs and liquid scintillation analysis indicated that although DMPT may have some limitations of chemical distribution within the embryo, these limitations are not sufficient to explain its teratogenic organotropism.

Animals↗
PubMed1991

Detection of acrolein and crotonaldehyde DNA adducts in cultured human cells and canine peripheral blood lymphocytes by 32P-postlabeling and nucleotide chromatography.

People are constantly being exposed to toxic and carcinogenic aldehydes. However, little is actually known about the mechanisms underlying the toxic and carcinogenic effects of these aldehydes on human cells. The DNA alkylating activities of two of the more toxic and environmentally prominent alpha,beta-unsaturated aldehydes, acrolein and crotonaldehyde, have been studied utilizing 32P-postlabeling and nucleotide chromatographic techniques. Several putative adducts were observed in DNAs isolated from acrolein- and crotonaldehyde-treated human fibroblasts. One of these acrolein-DNA adducts was tentatively identified as the cyclic 1,N2-hydroxypropanodeoxyguanosine product, 3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2- a]purine-10-one, by co-chromatography with a chemical standard. The 1,N2-hydroxypropanodeoxyguanosine along with other possible adducts, was also found in DNA isolated from peripheral blood lymphocytes obtained from a dog 1 h after receiving a therapeutic dose of 6.6 mg/kg of cyclophosphamide. These results not only demonstrate the presence of acrolein and crotonaldehyde DNA adducts in treated human cells, but also suggest that these sensitive techniques may be useful to the study of the importance of acrolein to both the carcinogenic and antineoplastic activities of cyclophosphamide and other oxazaphosphorine mustards.

Acrolein↗
PubMed1989

Teratogenicity of 3,3-dimethyl-1-phenyltriazene in the rat: gross malformations including micrognathism.

3,3-Dimethyl-1-phenyltriazene (DMPT), an alkylating agent, has been reported to be teratogenic in chickens, mice, and rats. One of the most commonly affected structures is the mandible; however, a complete description and incidence rates of all malformations produced have not been published. Rats were treated on day 12 of gestation (day 0 = sperm in vaginal smear) with a single intraperitoneal injection of 30 mg DMPT/kg. Fetuses were examined on each subsequent day of gestation for external and skeletal abnormalities. Standard soft tissue examinations were performed on day-20 fetuses. A high percentage (greater than or equal to 80%) of treated litters contained numerous fetuses with micrognathism, cleft palates, syndactyly, adactyly, and misshapen digits and limbs. Lordosis, cerebellar and cerebral hypoplasia, decreased fetal size, and generalized delayed ossification were also observed. Dams exposed to DMPT had decreased food consumption and weight gains, although clinicopathologic and histopathologic evaluations failed to indicate other evidence of maternal toxicity. DMPT caused numerous permanent structural alterations that were not attributed to maternal toxicity.

Abnormalities, Drug-Induced↗
PubMed1989

Teratogenicity of 3,3-dimethyl-1-phenyltriazene in the rat: histopathologic and ultrastructural alterations.

3,3-Dimethyl-1-phenyltriazene (DMPT) is a methylating agent which is teratogenic, carcinogenic, and mutagenic. A single intraperitoneal injection of 30 mg DMPT/kg given to pregnant rats on day 12 of gestation produces malformations with minimal maternal toxicity. Malformations include skeletal deformities such as micrognathism, cleft palate, and digital malformations, as well as central nervous system hypoplasia. The purpose of the present study was to characterize the light and electron microscopic alterations produced by DMPT. Electron microscopy (EM) revealed that at 4 hr postinjection of DMPT, rare cells of the neural tube contained few membrane-bound aggregations of organelles and condensed chromatin; this change was consistent with apoptosis, a type of cell death characterized by morphologic and biochemical alterations distinct from necrosis. At 8 hr postinjection, apoptosis was more prominent in the neural tube and also observed in the mandibular process. At 16 hr postinjection, numerous apoptotic cells were interspersed with unaffected cells that contained phagocytized apoptotic bodies. Light microscopic examination of DMPT-exposed conceptuses showed apoptosis in the neural tube at 24 hr postinjection. Forty-eight hours postinjection, apoptosis, in decreasing order of severity, was observed in the neural tube, craniofacial processes, limb buds, and somites and liver. Apoptosis was absent in all tissues by 72 hr postinjection. Nervous tissues failed to achieve proper histologic organization, but all other tissues appeared microscopically normal from 72 hr postinjection until the end of gestation. There appeared to be some degree of tissue specificity to the effects of DMPT.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Comparative toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), in chickens, quails, and turkeys.

Coniine, an alkaloid of Conium maculatum (poison hemlock), was administered by gavage to immature chickens, quails, and turkeys at 0, 25, 50, and 100 mg/kg body weight. At 25 mg coniine/kg body weight, clinical signs were observed only in quails (2/10) and consisted of excitement, depression, hypermetria, seizures, opisthotonos, and flaccid paralysis. Chickens (9/10) and quails (8/10) dosed at 50 mg/kg body weight were affected, and several birds of each species died (2/10 and 5/10, respectively). Turkeys (7/10) were affected only when dosed at 100 mg/kg body weight, and quails (6/10), turkeys (4/10), and chickens (10/10) died at this dose. There were no gross or microscopic lesions. Coniine was detected in skeletal muscle and liver of birds dying after ingestion and was present in some survivors 7 days post-treatment.

Alkaloids↗