Xenobiotic-metabolizing enzymes in human respiratory nasal mucgsa

Gervasi, P.G.; Longo, Vincenzo; Naldi, F.; Panattoni, Gian Luigi; Ursino, Francesco

doi:10.1016/0006-2952(91)90474-j

Cited by 72 publications

(34 citation statements)

References 27 publications

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“…Within the olfactory regions, the nasal airflow pattern determines the pattern of olfactory mucosal injury from inhaled NA. High rates of NA bioactivation by nasal microsomes raises the possibility that the nasal tissue of humans may be an injury target of NA since significant expression/activity of P450s in the nasal mucosa have been reported in humans (Longo et al, 1989;Gervasi et al, 1991;Gu et al, 2000;Su et al, 2000;Chen et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

In Situ Naphthalene Bioactivation and Nasal Airflow Cause Region-Specific Injury Patterns in the Nasal Mucosa of Rats Exposed to Naphthalene by Inhalation

Lee¹,

Phimister²,

Morin³

et al. 2005

J Pharmacol Exp Ther

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Despite the fact that naphthalene (NA), a volatile, ubiquitous air pollutant, was recently identified as a probable human carcinogen, little is known about nasal cytotoxicity from inhaled NA. To define and compare acute nasal injury from inhalation and systemic NA exposures, male Sprague-Dawley rats were exposed to filtered air; 3.4 or 23.8 ppm NA by inhalation for 4 h; or to 0, 25, 50, 100, or 200 mg/kg NA via intraperitoneal injection. Severe cellular injury occurred exclusively in the olfactory mucosa 24 h postinhalation exposure to 3.4 ppm NA for 4 h. This level is significantly below both the current Occupational Safety and Health Administration standard (10 ppm; 8 h) for NA and the lowest observed adverse effect level (10 ppm; 2 years) for the incidence of rat olfactory neoplasms. Injury within the olfactory mucosa from inhaled NA was confined to the medial meatus, whereas systemic NA generated severe injury throughout the olfactory region. The pattern of nasal injury from inhaled NA in this study is consistent with previous studies of nasal airflow simulation within the olfactory region. The nonolfactory mucosa on the nasal septum, a high airflow region, metabolized naphthalene slowly, whereas the olfactory regions of the nasal septum and ethmoturbinates metabolized this substrate at high rates. This study concludes that 1) the incidence of acute nasal injury from systemic and inhaled NA correlates with the rates of regional microsomal NA metabolism and that 2) the nasal airflow pattern determines the pattern of olfactory mucosal injury from inhaled NA.

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Section: Discussionmentioning

confidence: 99%

In Situ Naphthalene Bioactivation and Nasal Airflow Cause Region-Specific Injury Patterns in the Nasal Mucosa of Rats Exposed to Naphthalene by Inhalation

Lee¹,

Phimister²,

Morin³

et al. 2005

J Pharmacol Exp Ther

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“…The NM of humans, like that of rodents, has xenobiotic biotransformation capability (Gervasi et al, 1991;Wong et al, 2005). Importantly, where comparisons have been made (Feng et al, 1990;Li et al, 1992), rodent NM has higher biotransformation activity than does human.…”

Section: Human Effects Of Rodent Nasal Carcinogensmentioning

confidence: 99%

“…Species differ in their specific levels of biotransformation capability (Hadley and Dahl, 1983;Thornton-Manning and Dahl, 1997). Relatively little is known about NM biotransformation activity in humans, but biotransformation enzymes are definitely present (Gervasi et al, 1991;Lewis et al, 1994;Yokose et al, 1999;Zhang et al, 2005). Comparisons of rodent and human nasal tissues generally reveal the former to have higher biotransformation activities (Feng et al, 1990;Bogdanffy et al, 1998;Heydens et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Nasal Cytotoxic and Carcinogenic Activities of Systemically Distributed Organic Chemicals

2006

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Toxicity and carcinogenicity in the mucosa of the nasal passages in rodents has been produced by a variety of organic chemicals which are systemically distributed. In this review, 14 such chemicals or classes were identified that produced rodent nasal cytotoxicity, but not carcinogenicity, and 11 were identified that produced nasal carcinogenicity. Most chemicals that affect the nasal mucosa were either concentrated in that tissue or readily activated there, or both. All chemicals with effects in the nasal mucosa that were DNA-reactive, were also carcinogenic, if adequately tested. None of the rodent nasal cytotoxins has been identified as a human systemic nasal toxin. This may reflect the lesser biotransformation activity of human nasal mucosa compared to rodent and the much lower levels of human exposures. None of the rodent carcinogens lacking DNA reactivity has been identified as a nasal carcinogen or other cancer hazard to humans. Some DNA-reactive rodent carcinogens that affect the nasal mucosa, as well as other tissues, have been associated with cancer at various sites in humans, but not the nasal cavity. Thus, findings in only the rodent nasal mucosa do not necessarily predict either a toxic or carcinogenic hazard to that tissue in humans.

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“…Of these, CYP2E1 reacts with nitrosamine which is found in preserved foodstuffs. Inhaled xenobiotics and procarcinogens present in smoked foodstuffs may be activated by the oxidative and non-oxidative enzymes present in nasopharynx; thus contribute to the formation of NPC (82,83,99,100). The absence of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) may also increase the risk.…”

Section: Cytochrome P450 2e1mentioning

confidence: 99%

Higher incidence of nasopharyngeal carcinoma in some regions in the world confers for interplay between genetic factors and external stimuli

Chattopadhyay

Das

Chatterjee³

et al. 2017

DD&T

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Xenobiotic-metabolizing enzymes in human respiratory nasal mucgsa

Cited by 72 publications

References 27 publications

In Situ Naphthalene Bioactivation and Nasal Airflow Cause Region-Specific Injury Patterns in the Nasal Mucosa of Rats Exposed to Naphthalene by Inhalation

In Situ Naphthalene Bioactivation and Nasal Airflow Cause Region-Specific Injury Patterns in the Nasal Mucosa of Rats Exposed to Naphthalene by Inhalation

Nasal Cytotoxic and Carcinogenic Activities of Systemically Distributed Organic Chemicals

Higher incidence of nasopharyngeal carcinoma in some regions in the world confers for interplay between genetic factors and external stimuli

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