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Dissertation
Induction of DNA damage by topical application of spermicides and microbicides: consequences to viral pathogenesis
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2008
DOI:
https://doi.org/10.17918/etd-2965
Abstract
Among women's sexual health threats are disproportionate susceptibility to sexually transmitted disease (STD) and the possible lubrication of cervical barriers such as male condoms with nonoxynol-9 (N-9), which may enhance human immunodeficiency type 1 (HIV-1) transmission. Strategies for prevention of STD are insufficient to combat HIV-1 and other STD infections. Existing intervention strategies have deficiencies. Condoms/abstinence does not guarantee protection. Gardasil®, Human papillomavirus (HPV) vaccine does not cover all strains. STD has a higher societal cost. In the United States, STD treatment including HPV is over $8.4 billion annually. Topical microbicides therefore as our "new hope" are needed to fill this "gap" in order to control STD morbidity and mortality. Development of a female-friendly spermicide/microbicide is a priority with its ability to replace N-9 as a spermicide of choice in male latex condoms and perhaps with product expansion as a spermicide/microbicide personal lubricant. We compared the known N-9 used over 50 years for its contraceptive role with an alkyl sulfate, sodium dedocyl sulfate (SDS); a candidate microbicide. These two compounds disrupt cellular membranes, but SDS has additional property of chaotropism and protein denaturant. SDS also inactivates non-enveloped viruses such as HPV and other enveloped viruses in vitro and has broad antiviral and antibacterial activities than N-9. We examined the DNA damaging levels and recovery effects of the tested compounds using the alkaline comet assay. Moreover, we tested the hypothesis that N-9 associated DNA damage may facilitate HPV integration into the host genome and therefore increase the risk of cervical cancer. We assessed HPV DNA integration by determining viral sequences in the host genome using PCR and integrated HPV-16 PCR. 0.01% (0.162 mM) N-9 causes relatively more DNA damage than 0.01% (0.162 mM) SDS in HeLa cells as evidenced by the comet assay. As a new comparator for topical spermicides/microbicides, measuring DNA damage and repair is a novel way to evaluate these compounds. Evaluating formulations therefore under the sametesting conditions can help to distinguish between potential compounds likely to show promise as safe microbicides. SDS may prove safer than N-9 as a spermicide or microbicide.
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Details
- Title
- Induction of DNA damage by topical application of spermicides and microbicides
- Creators
- Joseph Owusu-Boateng - DU
- Contributors
- Mary K. Howett (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Bioscience and Biotechnology [Historical]; College of Arts and Sciences; Drexel University
- Other Identifier
- 2965; 991014632331804721