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Diana Anderson

Publications and source records attributed to Diana Anderson.

24 records · Page 2Linked to original sources
PubMed2003

The effect of the antioxidant catalase on oestrogens, triiodothyronine, and noradrenaline in the Comet assay.

Metabolic changes in the phenolic groups of steroidal oestrogens accompanied by the generation of quinones and reactive oxygen species underlie their mutagenic effects. Although nonsteroidal hormones and related compounds have not been thoroughly investigated for genotoxicity, some of them also contain phenolic groups that could be involved in redox cycling. Therefore, the aim of the present study was to evaluate the possible DNA damaging effects of the thyroid hormone, triiodothyronine (T3), and the neurotransmitter, noradrenaline (NA), in human lymphocytes using the Comet assay. After dose-response investigations, doses of 100 microM T3 and 550 microM of NA, producing clear DNA damaging effects and good cell viability, were chosen for further experiments with the antioxidant, catalase. Since the scavenging enzyme catalase reduced the DNA damaging effects of T3 and NA, it can be concluded that T3 and NA induced DNA damage mainly via the production of reactive oxygen species. Therefore, the mechanism of mutagenic action of both steroidal hormones and nonsteroidal compounds, T3 and NA, imply the creation of oxidative stress and subsequent DNA damage with reactive oxygen species and, possibly, with reactive hormone derivatives created during their redox cycling.

Adult↗
PubMed2003

Oestrogenic compounds and oxidative stress (in human sperm and lymphocytes in the Comet assay).

Reactive oxygen species (ROS) are produced by a wide variety of chemicals and physiological processes in which enzymes catalyse the transfer of electrons from a substrate to molecular oxygen. The immediate products of such reactions, superoxide anion radicals and hydrogen peroxide can be metabolised by enzymes such as superoxide dismutase (SOD) and catalase (CAT), respectively, and depending on its concentration by Vitamin C (Vit C). Under certain circumstances the ROS form highly reactive hydroxyl radicals. We examined human sperm and lymphocytes after treatment with six oestrogenic compounds in the Comet assay, which measures DNA damage, and observed that all caused damage in both cell types. The damage was diminished in nearly all cases by catalase, and in some instances by SOD and Vit C. This response pattern was also seen with hydrogen peroxide. This similarity suggests that the oestrogen-mediated effects could be acting via the production of hydrogen peroxide since catalase always markedly reduced the response. The variable responses with SOD indicate a lesser involvement of superoxide anion radicals due to SOD-mediated conversion of superoxide to hydrogen peroxide generally causing a lower level of DNA damage than other ROS. The variable Vit C responses are explained by a reduction of hydrogen peroxide at low Vit C concentrations and a pro-oxidant activity at higher concentrations. Together these data provide evidence that inappropriate exposure to oestrogenic compounds could lead to free-radical mediated damage. It is believed that the observed activities were not generated by cell free cell culture conditions because increased responses were observed over and above control values when the compounds were added, and also increasing dose-response relationships have been found after treatment with such oestrogenic compounds in previously reported studies.

Adult↗
PubMed2003

Aneugenic and clastogenic effects of doxorubicin in human lymphocytes.

Doxorubicin, a benzanthroquinone anticancer agent, was examined for its effect on micronucleus induction in cultured human lymphocytes. A statistically significant dose-dependent increase in micronucleus frequency (P<0.001) in binucleated cells was seen and an increase in the kinetochore-positive (P<0.001) and kinetochore-negative micronuclei (P<0.001) was observed. An increase was also observed in the number of necrotic cells, but the frequency of apoptotic cells remained almost constant. This confirms that doxorubicin is both clastogenic and aneugenic.

Adult↗
PubMed2002

Survey of public information about ongoing clinical trials funded by industry: evaluation of completeness and accessibility.

OBJECTIVE: To evaluate the completeness and accessibility of public information about US clinical trials of drugs in development. DESIGN: Review of online registers of clinical trials. DATA SOURCES: Drugs in phase III trials were identified using three drug industry sources: PhRMA Survey, What's in the Pipeline, and the NDA Pipeline. Drug trials were then searched for on the following publicly accessible registers of clinical trials:, and registers associated with the 37 "Comprehensive Cancer Centers" designated by the National Cancer Institute. MAIN OUTCOME MEASURE: Extent of availability of public information on phase III trials of drugs in development for treating either prostate or colon cancer. RESULTS: Search of industry sources identified 12 drugs for prostate cancer and 20 for colon cancer undergoing phase III trials. The most comprehensive publicly available register, contained trial listings for only seven of the prostate cancer drugs and 10 of the colon cancer drugs. Trials of three prostate cancer and three colon cancer drugs were listed on only one register each. A substantial proportion of trials of prostate cancer drugs (3/12) and colon cancer drugs (8/20) were not associated with trial listings in any registers. CONCLUSIONS: Existing trials registers are unlikely to be meeting user needs since many ongoing drug trials are not listed. There is a clear need for a comprehensive clinical trials register encompassing all ongoing trials, including industry sponsored trials.

Antineoplastic Agents↗
PubMed2002

Evaluation of the antigenotoxic potential of monomeric and dimeric flavanols, and black tea polyphenols against heterocyclic amine-induced DNA damage in human lymphocytes using the Comet assay.

The polyphenolic dimers, epicatechin-4beta-8-catechin (B1), epicatechin-4beta-8-epicatechin (B2), catechin-4beta-8-catechin (B3), catechin-4beta-8-epicatechin (B4), and the gallate ester epicatechin-4beta-8-epicatechin gallate (B'2G) were isolated from grape seeds, and theaflavins and theafulvins from black tea brews. The ability of these naturally-occurring polyphenols to afford protection against the genotoxicity of the heterocyclic amine 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was compared with that of the monomeric tea flavanols, (+)-catechin (C), (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG). Genotoxic activity was evaluated in human peripheral lymphocytes using the Comet assay. At the concentration range of 1-100 microM, neither the monomeric nor the dimeric flavanols prevented the lymphocyte DNA damage induced by Trp-P-2. In contrast, both of the black tea polyphenols, theafulvins and theaflavins, at a dose range of 0.1-0.5 mg/ml, prevented, in a concentration-dependent manner, the DNA damage elicited by Trp-P-2. Finally, neither the monomeric and dimeric polyphenols (100 microM) nor the theafulvins and theaflavins (0.5mg/ml) caused any DNA damage in the human lymphocytes. These studies illustrate that black tea theafulvins and theaflavins, if absorbed intact, may contribute to the anticarcinogenic potential associated with black tea intake.

Antimutagenic Agents↗