Roles Of Nitric Oxide In Neoplastic Transformation: The Effects Of NO Donors And Specific iNOS Inhibitors

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2014-01-15
Authors
Motosue, Alison
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Lesoon-Wood, Leslie
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Biology
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University of Hawaii at Manoa
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Nitric oxide (NO) is a gaseous radical compound involved in numerous physiological functions such as neurotransmission and fighting infection. It has also been shown to have mutagenic properties and there is some suggestion of its role in promoting carcinogenesis, as evidenced by previous work with iNOS inhibitors and antisense oligodeoxynucleotides. This study seeks to investigate NO's role in cytotoxicity and neoplastic transformation in C3H 10T1/2 mouse fibroblast cells. It was found that induction of endogenous NO by LPS/IFN-γ as well as exposure to exogenous NO donated by spermine NONOate or glycoSNAP-2 brought about cytotoxic effects. Moreover, inhibition of endogenous NO production by 1,4-PBIT reversed the cytotoxic effects of endogenous NO, while pre-treatment with LPS/IFN-γ or γ-tocopherol also prevented the cytotoxic effects of exogenous NO. NO seems to have a significant role in neoplastic transformation, not evidenced by the NO donors so much as by the NO inhibitors, which drastically reduced the severity of transformation.
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ii, 27 pages
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