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T Rowe

Publications and source records attributed to T Rowe.

60 records · Page 4Linked to original sources
PubMed1985

Inhibition of epipodophyllotoxin cytotoxicity by interference with topoisomerase-mediated DNA cleavage.

This laboratory and others previously proposed that the antitumor effects of the epipodophyllotoxin compounds are based on their abilities to stimulate DNA cleavage by a DNA topoisomerase. To explore this relationship further, we studied the intercalating agent ethidium bromide and found that it blocked epipodophyllotoxin-induced DNA cleavage by DNA topoisomerase II in vitro as well as in vivo. Using an in vitro assay consisting of purified calf thymus DNA topoisomerase II, end-labeled DNA, and the epipodophyllotoxin teniposide, we found that ethidium bromide markedly interfered with the enzyme-mediated DNA cleavage. Furthermore, ethidium bromide also blocked the formation of DNA single- and double-strand breaks in mouse L1210 cells when exposed to the epipodophyllotoxin etoposide. This effect cannot be explained by alterations in drug accumulation since steady-state drug concentrations were unchanged, and the effect was also observed in isolated nuclei. In addition to its effects on epipodophyllotoxin-mediated DNA breakage, ethidium bromide also potently inhibited the cytotoxic effects of etoposide but only when present during drug treatment. Thus, we believe that ethidium bromide may be a useful tool to investigate drug-induced perturbations of topoisomerase activity and their relationship to antitumor effect. Our data strongly support the hypothesis that the antitumor activity of epipodophyllotoxins is based on the ability to stimulate the formation of a cleavable complex between DNA topoisomerase and DNA.

Animals↗
PubMed1984

Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage.

Epipodophyllotoxins are an important new class of anticancer agents which include the compounds VM-26 (teniposide) and VP-16 (etoposide). The mechanism of action of these drugs appears to involve production of DNA single- and double-strand breaks by virtue of a temperature-sensitive interaction between drug and a heat-labile intranuclear component. We now report evidence indicating that type II topoisomerase is the likely intracellular target for the DNA strand-breaking effects of the epipodophyllotoxins. Both VM-26 and VP-16 stimulate site-specific DNA cleavage by a highly purified calf thymus type II topoisomerase. VM-26 is 5- to 10-fold more potent than VP-16 in this assay, a difference that is also seen when DNA strand breaks are assayed in isolated nuclei of mouse leukemia cells following drug exposure. Furthermore, a similar potency difference exists with respect to cytotoxicity. Equilibrium dialysis experiments using [3H]VP-16 indicate that the drug does not bind to DNA. Thus, we suggest that the epipodophyllotoxins exert their anti-cancer effects by "poisoning" type II topoisomerase without binding to DNA. In this regard, their actions may be analogous to those of nalidixic acid in bacteria.

Animals↗
PubMedDate not supplied

Massive intracranial immature teratoma with extracranial extension into oral cavity, nose, and neck.

We present a case of congenital massive intracranial teratoma with extracranial extension into oral cavity, nose, and neck diagnosed by antenatal ultrasonography at 25 weeks of gestation. The fetus was delivered by cesarean section because of massive fetal head size and severe maternal pregnancy-induced hypertension. At necropsy the tumor was found to be an immature teratoma, with no recognizable normal brain tissue. An additional finding was hepatomegaly secondary to extensive extramedullary hematopoiesis. Karyotyping of both the fetus and the teratoma revealed a normal female chromosomal composition: 46,XX.

Adolescent↗
PubMedDate not supplied

Prevalence of Salmonella serotypes on pig carcasses from high- and low-risk herds slaughtered in three abattoirs.

The aim of this study was to compare the prevalence of Salmonella serotypes at two different sites on pig carcasses from herds classified as high-risk or low-risk and to elucidate the relationship between carcass contamination levels and serological status. Caecal samples and carcass surface swabs were cultured for Salmonella from a total of 210 pigs from low risk herds (< 19% of pigs in herd Salmonella seropositive) and 209 pigs from high risk herds (> 32% of pigs in herd Salmonella seropositive) in three abattoirs. Meat juice samples were collected for analysis by ELISA. The prevalence of Salmonella in the caecal contents of "low-risk" pigs was 10%, which was significantly lower than the 19% prevalence in "high-risk" pigs (p < 0.01). The corresponding figures for skin samples collected immediately post-evisceration were 2% and 12%. The predominant Salmonella serotype in the caecal contents of both the low-risk and high-risk pigs was Salmonella Typhimurium. Salmonella Kentucky and Salmonella Derby were the most frequent isolates from the carcass surface swabs of low- and high-risk pigs respectively. There was a positive association between seropositivity of pigs from high-risk herds and caecal carriage (p < 0.05). Results showed that herd categorisation based on serological results was useful in predicting Salmonella isolation rates from caecal samples and surface swabs of slaughtered pigs.

Abattoirs↗