Styrene Respiratory Tract Toxicity and Mouse Lung Tumors Are Mediated by CYP2F-Generated Metabolites

Cruzan, George; Carlson, Gary P.; Johnson, Keith A.; Andrews, Larry S.; Banton, Marcy I.; Bevan, Christopher; Cushman, Janette R.

doi:10.1006/rtph.2002.1545

Cited by 73 publications

(41 citation statements)

References 56 publications

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“…Our result is consistent with the findings reported by Carlson; that there are no differences in in vivo toxicity of styrene oxide between the CYP2E1 knockout mice and the wild type (Carlson, 2003(Carlson, , 2004c. Recent studies showed that styrene respiratory tract toxicity in mice and rats, including mouse lung tumors, are mediated by CYP2F (Cruzan et al, 2002). CYP2B was also reported to play a minor role in styrene metabolism (Carlson et al, 1998).…”

Section: Resultssupporting

confidence: 95%

Investigation of bioactivation and toxicity of styrene in CYP2E1 transgenic cells

Chung¹,

Wei²,

Liu³

et al. 2006

Toxicology

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Section: Resultssupporting

confidence: 95%

Investigation of bioactivation and toxicity of styrene in CYP2E1 transgenic cells

Chung¹,

Wei²,

Liu³

et al. 2006

Toxicology

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“…Exceptions to the trend described above have been observed in a few instances. For example, mice are far more sensitive to olfactory cytotoxic damage following exposure to styrene than rats (Cruzan et al, 1999;Green et al, 2001). O-nitrotoluene caused tissue lesions and tumors at multiple sites, but not the olfactory mucosa, in rats, while the only lesion found in mice exposed to 625-10,000 ppm of o-nitrotoluene for 13-weeks was a dose-related increase in olfactory mucosal degeneration (Dunnick et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Strain-Specific Effects of Alachlor on Murine Olfactory Mucosal Responses

2004

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Chloracetanilide herbicides are multisite carcinogens in rodents. Progression of alachlor-induced olfactory tumors in rats is accompanied by cytoplasmic accumulation and nuclear localization of β-catenin, suggesting activation of Wnt signaling. Female CD-1 mice were resistant to alachlorinduced olfactory carcinogenesis. The current studies were performed to determine whether Apc Min/+ mice, which have activated Wnt signaling due to mutation of the second allele of Apc, would be susceptible to alachlor olfactory carcinogenesis. Female and male Apc Min/+ mice, as well as Apc +/+ littermates received alachlor in the diet (260 mg/kg/d) for up to 3 months. Female A/J and C57BL/6J wild-type mice were also treated (for 10 and 14 months, respectively), as these strains vary in sensitivity to many respiratory tract insults. No olfactory mucosal tumors were observed in any of the mice, although alachlor-treated Apc Min/+ mice developed histological changes similar to those in alachlor-treated rats. Alachlor-treated A/J mice developed pronounced intracellular accumulation of amorphous eosinophilic material in the olfactory mucosa, foci of respiratory-like metaplasia, and hyperplasia of nasal mucus glands. A similar but less intense response was seen in C57BL/6J mice. Mice and rats had equivalent levels of the putative bioactivating enzyme (CYP2A) in olfactory mucosa, and mice had induced hepatic CYP3A and CYP2B enzymes with alachlor treatment, which may increase alachlor elimination. These studies extend previous observations by describing alachlor-induced olfactory mucosal changes in mice and suggest that hepatic metabolic enzyme induction may be responsible for resistance of mice to alachlor-induced olfactory carcinogenesis.

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“…In mice, rats, and humans, styrene is converted to styrene oxide by CYP2E1 and CYP2F2. Articles by Cruzan et al (2002Cruzan et al ( , 2005a noted that in the mouse, CYP2F2 is also involved in the production of 4-vinylphenol, a styrene metabolite reported to be more potent than styrene oxide in inducing pulmonary toxicity. Inhibition of CYP2F2 by 5-phenyl-1-pentyne blocked styrene-induced pulmonary toxicity in mice.…”

Section: Genetic Toxicitymentioning

confidence: 97%

NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of styrene

Luderer

Collins

Daston

et al. 2005

Birth Defects Research Pt B

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Styrene Respiratory Tract Toxicity and Mouse Lung Tumors Are Mediated by CYP2F-Generated Metabolites

Cited by 73 publications

References 56 publications

Investigation of bioactivation and toxicity of styrene in CYP2E1 transgenic cells

Investigation of bioactivation and toxicity of styrene in CYP2E1 transgenic cells

Strain-Specific Effects of Alachlor on Murine Olfactory Mucosal Responses

NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of styrene

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