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Biomedical subjects

S S Epstein

Publications and source records attributed to S S Epstein.

At least 73 records · Page 4Linked to original sources

DNA repair synthesis in guineapig pancreas following exposure to nitrosomethylurethane.

NMUT, a known pancreatic carcinogen in guineapigs, alkylates pancreatic DNA and RNA, both in vivo and in vitro. Following the in vivo administration of a single maximum tolerated dose of NMUT (30 mg/kg), a significant increase in 3H-Tdr incorporation into DNA was observed in the duodenal segment of the pancreas after four days; this increase in thymidine incorporation probably represents in vivo DNA repair synthesis. The level of normal DNA synthesis was greater in the duodenal segment than elsewhere in the pancreas. In vitro exposure of pancreatic slices from the duodenal segment to 20 mM NMUT for 30 minutes resulted in a significant increase in 3H-TdR incorporation into DNA in the presence of HU, reflecting DNA repair synthesis following NMUT-induced DNA damage; normal DNA synthesis in the pancreatic slices in vitro was markedly suppressed by 10 mM HU. Studies on the kinetics of DNA repair synthesis in pancreatic slices indicated an initial increase of 3H-TdR incorporation, followed by a steady time-dependent decline. It appears that most of the DNA repair synthesis occurs within two hours after exposure to NMUT.

Animals↗

Prenatal and postnatal toxicity induced in guinea-pigs by nitrosomethylurea.

Oral administration of NMU at maximally tolerated doses of guinea-pigs from day 34 to 58 of pregnancy induced embryotoxic effects, as evidenced by a high incidence of stillbirths and reduction in birth weight, and postnatal toxic effects, as evidenced by stunting, progressive mortality and extensive fatty degeneration of the liver in F1 progeny. Similar administration of NMUT at maximally tolerated doses did not induce such toxic effects.

Animals↗

Evidence of repair of DNA damage induced by 4-hydroxyaminoquinoline 1-oxide in guinea pig pancreatic slices in vitro.

In vitro exposure of guinea pig pancreatic slices to 4-hydroxyaminoquinoline 1-oxide (HAQO) resulted in increased [methyl-3H]thymidine ([3H]TdR) incorporation into DNA, both in the presence and absence of hydroxyurea (HU). Normal DNA replicative synthesis, but not DNA repair synthesis, was suppressed by HU. The increase in [3H]TdR incorporation into DNA damage induced by HAQO. Exposure of pancreatic slices to 10(-6) to 10(-5) M concentrations of HAQO did not significantly increase thymidine incorporation; however, a 15-min exposure to 10(-4) M HAQO induced a significant increase in HU-insensitive [3H]TdR incorporation into DNA. Kinetics of [3H]TdR incorporation suggests that most of the DNA repair synthesis occurs during the 2 hr following HAQO-induced DNA damage.

4-Hydroxyaminoquinoline-1-oxide↗

Pre- and postnatal toxicity induced in guinea pigs by N-nitrosomethylurea.

Oral administration of N-nitrosomethylurea at maximally tolerated doses to guinea pigs on alternate days from days 34-58 of pregnancy induced prenatal toxicity, as evidenced by a high frequency of stillbirths and intrauterine growth retardation, and postnatal toxicity, as evidenced by stunting and progressive mortality. Similar administration of N-nitrosomethylurethane at maximally tolerated doses did not induce such toxic effects.

Abnormalities, Drug-Induced↗

Effects of ingested chrysotile on DNA synthesis in the gastrointestinal tract and liver of the rat.

The effects of chrysotile on DNA synthesis in the gastrointestinal tract of the rat were studied by measuring the uptake of tritium-labeled thymidine; whole stomach, small intestine, colon liver were removed, cleaned, and homogenized and the DNA was isolated and assayed for tritium label.A dose-response study indicated that 2 weeks after a 5 mg/kg dose of chrysotile, DNA synthesis was increased in the small intestine and colon and reduced in the liver; synthesis was reduced in the small intestine 2 weeks after a 500 mg/kg dose. Following a 100 mg/kg dose of chrysotile, a transient increase in DNA synthesis was noted in the stomach and small intestine at 1 and 7 days, respectively, besides increased synthesis in the colon from 28 to 63 days. These data suggest that asbestos penetrates the gastrointestinal mucosa and influences regulation of DNA synthesis in the gastrointestinal tract.

Administration, Oral↗