Several short-term assays are in use to assess the carcinogenic hazard of chemicals. While the ability to induce initiating events that may lead to carcinogenesis is measured, compounds and conditions that might modify the ability of chemicals to cause those initiating events are not assessed by such tests. In addition, compounds that affect the ability of cells to react in a normal fashion to the damaging action of carcinogens are not detected by these methods.
Shifts in alkaline sucrose gradient profiles of centrifuged DNA (as an indication of DNA fragmentation) and formation of aryl and alkyl DNA adducts (as an indication of DNA modification) have been used as short-term assays for carcinogenic and mutagenic potential. Repair of DNA damage has been measured by restoration of near-control sedimentation profiles of DNA and the loss of aryl and alkyl adducts over time after damage or modification of DNA by carcinogens and mutagens.
In this study, the ability of sodium ascorbate to modify the DNA fragmenting and adduct-forming action of the carcinogens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and benzo(a)pyrene (BP) was investigated. In addition, the ability of cells In vivo and In vitro to repair DNA in the presence of sodium ascorbate was assessed by the two methods described above.
It was found that sodium ascorbate inhibited repair in vivo and in vitro. In addition, sodium ascorbate was found to fragment DNA in vivo and in vitro in the presence of copper, and to inhibit the action of carcinogens _in vivo and in vitro by nucleophilic
scavenging of electrophilic carcinogens.
Sodium ascorbate was also found to inhibit the binding of BP to DNA jLn vivo and In vitro. On the other hand, other reducing agents had other effects. Propyl gallate (a sulphydryl reducing compound) inhibited binding of BP to DNA in vitro, but enhanced binding of BP to DNA in vivo. The sulphydryl reducing agent glutathione enhanced binding of BP to DNA in vivo and in vitro.
Alkaline sucrose gradient analysis of DNA damage and recovery from that damage, and BP adduct formation in DNA and disappearance over time, appear to be suitable methods for assessment of the modifying properties of compounds and conditions on the initiating events that may lead to mutation or carcinogenesis. / Medicine, Faculty of / Medical Genetics, Department of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/23081 |
| Date | January 1981 |
| Creators | Koropatnick, Donald James |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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