Increased susceptibility to parathion poisoning following murine cytomegalovirus infection

Selgrade, MaryJane K.; Daniels, Mary J.; Illing, Joseph W.; Ralston, Ann L.; Grady, Margaret A.; Charlet, Elaine; Graham, Judith A.

doi:10.1016/0041-008x(84)90017-6

Cited by 16 publications

(6 citation statements)

References 20 publications

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“…The interactions between HSV-1 infection and these enzymes have not been described thus far. Since murine cytomegaloviru s suppressed NADPH:cytochrome P450 through virus-induced interferon (Selgrade et al, 1984), it is feasible that HSV-1 may not increase expression of NADPH:cytocrome P450. In addition, glutathione S-transferase (GST) has been considered to be important in inactivation of MMC .…”

Section: Discussionmentioning

confidence: 99%

Combined Therapy with Chemotherapeutic Agents and Herpes Simplex Virus Type 1 ICP34.5 Mutant (HSV-1716) in Human Non-Small Cell Lung Cancer

Toyoizumi¹,

Abbas²,

Kang³

et al. 1999

Human Gene Therapy

107

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A replication-selective herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) has shown efficacy both in vitro and in vivo against human non-small cell lung cancer (NSCLC) cell lines but complete eradication of tumor has not been accomplished with a single viral treatment in our murine xenograft models. Therefore, strategies to enhance the efficacy of this treatment were investigated. We determined the oncolytic activity of HSV-1716 in NCI-H460 cells in combination with each of four chemotherapeutic agents: mitomycin C (MMC), cis-platinum II (cis-DDP), methotrexate (MTX), or doxorubicin (ADR). Isobologram analysis was performed to evaluate the interaction between the viral and chemotherapeutic agents. The oncolytic effect of HSV-1716 in combination with MMC was synergistic in two of five NSCLC cell lines. In the other three cell lines, the combined effect appeared additive. No antagonism was observed. The in vivo effect of this combination was then examined in a murine xenograft model. NCI-H460 flank tumors were directly injected with HSV-1716 (4 x 106 PFU) followed by intravenous MMC administration (0.17 mg/kg) 24 hr later. After 3 weeks, the mean tumor weight in the combined treatment group was significantly less than either individual treatment in an additive manner. The synergistic dose of MMC neither augmented nor inhibited viral replication in vitro and HSV-1716 infection did not upregulate DT-diaphorase, which is the primary enzyme responsible for MMC activation. In summary, the combination of HSV-1716 with common chemotherapeutic agents may augment the effect of HSV-based therapy in the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Combined Therapy with Chemotherapeutic Agents and Herpes Simplex Virus Type 1 ICP34.5 Mutant (HSV-1716) in Human Non-Small Cell Lung Cancer

Toyoizumi¹,

Abbas²,

Kang³

et al. 1999

Human Gene Therapy

107

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“…On the other hand, Kaminski et al (1990) demonstrated that aminoacetonitrile, a competitive inhibitor of cytochrome P-450, reversed carbon tetrachloride-mediated suppression of the T -dependent antibody response in mice. Furthermore, increased susceptibility to parathion poisoning due to a decrease in the ability of cytomegalovirusinfected mice to detoxify the insecticide was demonstrated (Selgrade et al, 1984). Finally, infections of several types have been shown to alter xenobiotic biotransformation in animals.…”

Section: Immunotoxicity and Neurotoxicitymentioning

confidence: 99%

Animal Biomarkers as Pollution Indicators

Peakall¹

1992

259

175

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“…Particularly unclear is the issue of the effect of OPs on the immune system. Numerous publications report on various changes in immunologic parameters subsequent to OP exposure, including changes in thymus and spleen weights (7)(8), reduction in the number and/or function ofB and T lymphocytes (9)(10), and decrease in host resistance to pathogens (11). Despite some recent excellent reviews on the topic (12), what remains unclear is whether the reported changes are the consequence of esterase inhibition and, as such, a class effect of OPs or the result of compound-specific effects unrelated to esterase inhibition, or a combination of the above.…”

Section: Organophosphatementioning

confidence: 99%

The Organophosphate Paraoxon Has No Demonstrable Effect on the Murine Immune System following Subchronic Low Dose Exposure

Azimullah

et al. 2008

Int J Immunopathol Pharmacol

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Paraoxon is the bioactive metabolite of the organophosphate pesticide parathion. Desulphuration of parathion by liver enzymes or sunlight results in the formation of paraoxon which inhibits acetylcholine esterase (AChE) activity. In the present study, we analyzed the effect of a 6-week, subchronic treatment with two different daily intraperitoneal doses (30 or 40 nmol) of paraoxon on the immune system of BALB/c mice. At a dose of 30 nmol/day, body weight of treated animals was unchanged compared to the controls. In contrast, the higher dose (40 nmol/day) induced a reduction in body growth, particularly in the first 3 weeks of treatment, peaking at week 2 when the saline group showed a 14.2-fold increase in body weight gain compared to paraoxon-treated animals. Moreover, mice treated with either dose of paraoxon had a >50% reduction in AChE activity during the first 3 weeks of treatment, but by the end of the treatment (week 6), AChE activity returned to normal. With regard to immunological parameters, there was no significant difference in either total spleen weight or in the ratios of various spleen cell populations between control and paraoxon-treated animals. Furthermore, no changes were observed in mitogen-induced cytokine secretion from splenocytes of paraoxon-treated mice. Finally, subchronic exposure to paraoxon did not alter mortality of mice exposed to a bacterial infection with Salmonella typhimurium. These data suggest that although subchronic exposure to paraoxon induced a transient inhibition in AChE activity, it had no demonstrable effect on the host immune system. Organophosphate(OP) compounds are extensively used as pesticides throughout the world. It has been estimated that 95% of fatal pesticide poisonings occur in developing countries each year, leading to around 220,000 deaths (1). A WHO task group estimated there may be one million serious, unintentional, pesticide poisonings each year and, on the basis of a survey of self-reported minor poisoning, estimated that there may be up to 25 million agricultural workers in the developing world suffering an episode of poisoning each year (2). Whilst the exact proportion of these poisonings that are due to OPs is unknown, it is believed to be substantial. In 1995 there were 15,300 cases of pesticide poisoning in China of which 91% were due to OPs (3), and in 1996 it was estimated that

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Increased susceptibility to parathion poisoning following murine cytomegalovirus infection

Cited by 16 publications

References 20 publications

Combined Therapy with Chemotherapeutic Agents and Herpes Simplex Virus Type 1 ICP34.5 Mutant (HSV-1716) in Human Non-Small Cell Lung Cancer

Combined Therapy with Chemotherapeutic Agents and Herpes Simplex Virus Type 1 ICP34.5 Mutant (HSV-1716) in Human Non-Small Cell Lung Cancer

Animal Biomarkers as Pollution Indicators

The Organophosphate Paraoxon Has No Demonstrable Effect on the Murine Immune System following Subchronic Low Dose Exposure

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