Prior to employing the Fischer 344 rat in teratology studies, it was considered necessary to establish the responsiveness of this strain to teratogenic agents. Bred Fischer 344 rats were administered 0, 3.2, 32, or 128 mg/kg/day (approximately 1,000, 10,000, or 40,000 USP units per animal) of vitamin A palmitate by gavage on days 6 through 15 of gestation. Maternal toxicity, as evidenced by decreased body weight gain, and decreased food and water consumption, was observed at the 128 mg/kg/day dose level. This dosage level was embryolethal and teratogenic in the Fischer 344 rat. The incidence of fetal resorptions was statistically significantly increased as compared to controls. Among the surviving fetuses, malformations observed included cleft palate, exencephaly, microphthalmia, anophthalmia, hydronephrosis, brachygnathia, pinna anomalies, and great vessel and heart anomalies. Based on these findings, it is concluded that the Fischer 344 rat responded to a known teratogenic agent and hence is appropriate for use in studies designed to evaluate the teratogenic potential of test agents.

Connective tissue-activating peptides (CTAPs) stimulate human synovial cells to exhibit a higher rate of DNA synthesis, glycolysis, and glycosaminoglycan formation. These bioactive peptides have been isolated from human platelets (CTAP-III), lymphocytes, tumor cells, and neutrophilic leukocytes. Several other growth factors, such as somatomedins A and C and nonsuppressible insulin-like activity (soluble), have been shown to be dependent on the circulating levels of pituitary GH. In this study, we examined the human GH (hGH) dependence of CTAP-III. Platelets from children with reduced or absent hGH were examined for the presence of CTAP-III. The peptide was detected qualitatively by polyacrylamide gel electrophoresis and Ouchterlony double diffusion. CTAP-III antigen, measured by RIA, was found in normal amounts in platelet lysates from normal persons and GH-deficient patients. Biological activity of the peptide was suggested by the ability of platelet lysates to stimulate the formation of glycosaminoglycans and increase sulfate incorporation into glycosaminoglycans formed in cell cultures. In addition, normal and hGH-deficient platelet lysates contained potent mitogenic activity which increased thymidine incorporation into DNA. Platelets from GH-deficient patients also released CTAP-III normally on exposure to thrombin.

In situ hybridization of Drosophila melanogaster somatic chromosomes has been used to demonstrate the near exact correspondence between the location of highly repetitious DNA and classically defined constitutive heterochromatin. The Y chromosome, in particular, is heavily labeled even by cRNA transcribed from female (XX) DNA templates (i.e., DNA from female Drosophila with 2 Xs and 2 sets of autosomes). This observation confirmes earlier reports that the Y chromosome contains repeated DNA sequences that are shared by other chromosomes. In grain counting experiments the Y chromosome shows significantly heavier label than any other chromosome when hybridized with cRNA from XY DNA templates (i.e., DNA from male Drosophila with 1 X and 1 Y plus 2 sets of autosomes). However, the preferential labeling of the Y is abolished if the cRNA is derived from XX DNA. We interpret these results as indicating the presence of a class of Y chromosome specific repeated DNA in D. melanogaster. The relative inefficiency of the X chromosome in binding cRNA from XY and XYY DNA templates, coupled with its ability to bind XX derived cRNA, may also indicate the presence of an X chromosome specific repeated DNA.

Male Fischer 344 rats were administered triethylenemelamine orally at dose levels of 0, 0.5 or 1.0 mg TEM/kg/day, five days per week for four weeks. A separate group of males was administered TEM as a single intraperitoneal injection of 0.3 mg/kg. Following treatment, males were mated with two groups of untreated females for a period of one week each. The uterine contents of untreated females were examined for evidence of a dominant lethal effect as manifested in an increase in the average resorption rate. Significant increases in the resorption rate were seen at 0.5 mg/kg/day for the second breeding period, and at 1.0 mg/kg/day for both breeding periods following oral administration. Significant decreases in the number of implantations, and increases in the average pre-implantation loss and resorption rate were observed following intraperitoneal administration. These effects seen in Fischer 344 rats were comparable to results obtained with other strains following a similar treatment regimen.

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