Dna breakage and inactivation resulting from hydroxylamine and/or cis-Diamminedichloroplatinum(Ii) interactions with plasmid dna

Rauko, P; Novotný, Ladislav; Balázová, E

doi:10.1016/0020-711x(93)90693-9

Cited by 5 publications

(3 citation statements)

References 13 publications

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“…However, base substitutions may not be the only cause of virion death. Hydroxylamine is also known to cause breaks in DNA and to cleave specific protein bonds, both of which will cause virion death (Rhaese and Freese 1968; Tessman 1968; Taylor et al 1970; Rauko et al 1993; Robins et al 2013). Thus, virion decay may be due to a combination of effects, only some of which are due to classic mutations.…”

Section: Resultsmentioning

confidence: 99%

Empirical Complexities in the Genetic Foundations of Lethal Mutagenesis

et al. 2013

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From population genetics theory, elevating the mutation rate of a large population should progressively reduce average fitness. If the fitness decline is large enough, the population will go extinct in a process known as lethal mutagenesis. Lethal mutagenesis has been endorsed in the virology literature as a promising approach to viral treatment, and several in vitro studies have forced viral extinction with high doses of mutagenic drugs. Yet only one empirical study has tested the genetic models underlying lethal mutagenesis, and the theory failed on even a qualitative level. Here we provide a new level of analysis of lethal mutagenesis by developing and evaluating models specifically tailored to empirical systems that may be used to test the theory. We first quantify a bias in the estimation of a critical parameter and consider whether that bias underlies the previously observed lack of concordance between theory and experiment. We then consider a seemingly ideal protocol that avoids this bias—mutagenesis of virions—but find that it is hampered by other problems. Finally, results that reveal difficulties in the mere interpretation of mutations assayed from double-strand genomes are derived. Our analyses expose unanticipated complexities in testing the theory. Nevertheless, the previous failure of the theory to predict experimental outcomes appears to reside in evolutionary mechanisms neglected by the theory (e.g., beneficial mutations) rather than from a mismatch between the empirical setup and model assumptions. This interpretation raises the specter that naive attempts at lethal mutagenesis may augment adaptation rather than retard it.

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Section: Resultsmentioning

confidence: 99%

Empirical Complexities in the Genetic Foundations of Lethal Mutagenesis

et al. 2013

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“…In addition, combined CDDP and hyperthermia is effective in the treatment of hypoxic tumor cells, unlike single‐modality radiation or chemotherapy 19 . Studies of CDDP binding to DNA have shown that hyperthermia induces more DNA adducts, contributes to increased tumor growth delay, and amplifies interstrand crosslinks by cisplatinum 24,41–43 . Together, these results provide strong evidence that synergistic effects of heat and cisplatinum are likely to improve therapeutic response of recurrent head and neck tumors following combined drug and laser treatment.…”

Section: Discussionmentioning

confidence: 98%

Laser and cisplatinum for treatment of human squamous cell carcinoma

et al. 1998

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“…Higher CDDP uptake after heating also enhances cytotoxicity in proliferating cancer cells and stimulates protein kinases to induce tumor apoptosis [18]. Studies of CDDP binding to DNA have shown that hyperthermia induces more DNA adducts, contributes to increased tumor growth delay, and amplifies interstrand crosslinks by cisplatinum [19][20][21][22][23]. Together, these results provide strong evidence that synergistic effects of heat and cisplatinum are likely to improve therapeutic response of recurrent head and neck tumors following combined drug and laser treatment.…”

Section: Discussionmentioning

confidence: 99%

Combined Cisplatinum and Laser Thermal Therapy for Palliation of Recurrent Head and Neck Tumors

Paiva

Saxton

Blackwell

et al. 1999

Diagnostic and Therapeutic Endoscopy

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In recent years endoscopically controlled laser-induced thermal therapy (LITT) has been increasingly accepted as a minimally invasive method for palliation of advanced or recurrent head and neck or gastrointestinal cancer. Previous studies have shown that adjuvant chemotherapy can potentiate endoscopic laser thermal ablation of obstructing tumors leading to improved palliation in advanced cancer patients. Eight patients with recurrent head and neck tumors volunteered to enroll as part of an ongoing phase II LITT clinical trial, and also elected to be treated with systemic chemotherapy (cisplatin, 80 mg/m2) followed 24 h later by palliative laser thermal ablation. Laser treatments were repeated in patients with residual disease or recurrence for a total of 27 LITT sessions. Four of the 8 patients treated with laser thermal chemotherapy remained alive after a median follow-up of 12 months. Of the 12 tumor sites treated, complete responses were located in the oral cavity (3), oropharynx (1), hypopharynx (1), maxillary sinus (1), and median survival for these patients was 9.5 months. This initial experience with cisplatinum-based laser chemotherapy indicates both safety and therapeutic potential for palliation of advanced head and neck cancer but this must be confirmed by longer follow-up in a larger cohort of patients.

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Dna breakage and inactivation resulting from hydroxylamine and/or cis-Diamminedichloroplatinum(Ii) interactions with plasmid dna

Cited by 5 publications

References 13 publications

Empirical Complexities in the Genetic Foundations of Lethal Mutagenesis

Empirical Complexities in the Genetic Foundations of Lethal Mutagenesis

Laser and cisplatinum for treatment of human squamous cell carcinoma

Combined Cisplatinum and Laser Thermal Therapy for Palliation of Recurrent Head and Neck Tumors

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