Genotoxicity induced in human lymphoblasts by atmospheric reaction products of naphthalene and phenanthrene

Sasaki, Jennifer C.; Arey, Janet; Eastmond, David A.; Parks, Karyn K.; Grosovsky, Andrew J.

doi:10.1016/s1383-5718(97)00083-1

Cited by 72 publications

(39 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…nitro-PAH (Sasaki et al, 1997), or less toxic. Heterogeneous reactions of particulate PAHs (Bertram et al, 2001;Esteve et al, 2003Esteve et al, , 2004Esteve et al, , 2006) may serve as surrogates for heterogeneous chemistry of many types of organics; such reactions could change the particles' hydrophilicity and thus their potential to act as cloud condensation nuclei (Jones et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Sources and transformations of particle-bound polycyclic aromatic hydrocarbons in Mexico City

et al. 2006

View full text Add to dashboard Cite

Abstract. Understanding sources, concentrations, and transformations of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere is important because of their potent mutagenicity and carcinogenicity. The measurement of particlebound PAHs by three different methods during the Mexico City Metropolitan Area field campaign in April 2003 presents a unique opportunity for characterization of these compounds and intercomparison of the methods. The three methods are (1) collection and analysis of bulk samples for time-integrated gas-and particle-phase speciation by gas chromatography/mass spectrometry; (2) aerosol photoionization for fast detection of PAHs on particles' surfaces; and (3) aerosol mass spectrometry for fast analysis of size and chemical composition. This research represents the first time aerosol mass spectrometry has been used to measure ambient PAH concentrations and the first time that fast, real-time methods have been used to quantify PAHs alongside traditional filter-based measurements in an extended field campaign. Speciated PAH measurements suggest that motor vehicles and garbage and wood burning are important sources in Mexico City. The diurnal concentration patterns captured by aerosol photoionization and aerosol mass spectrometry are generally consistent. Ambient concentrations of particlephase PAHs typically peak at ∼110 ng m −3 during the morning rush hour and rapidly decay due to changes in source activity patterns and dilution as the boundary layer rises, although surface-bound PAH concentrations decay faster. The more rapid decrease in surface versus bulk PAH concentraCorrespondence to: L. C. Marr (lmarr@vt.edu) tions during the late morning suggests that freshly emitted combustion-related particles are quickly coated by secondary aerosol material in Mexico City's atmosphere and may also be transformed by heterogeneous reactions.

show abstract

Section: Introductionmentioning

confidence: 99%

Sources and transformations of particle-bound polycyclic aromatic hydrocarbons in Mexico City

et al. 2006

View full text Add to dashboard Cite

show abstract

“…One potential mechanism of action for its carcinogenicity is demonstrated in assays that measure induction of clastogenic chromosomal effects. For example, naphthalene gave positive results in micronucleus assays (6,24) and chromosomal aberration (21) and recombination tests (5), consistent with a clastogenic mechanism of action. For some endpoints, naphthalene-induced chromosomal effects require, or are enhanced by, cytochrome P450 enzymes.…”

Section: Discussionmentioning

confidence: 91%

Morphology of Nasal Lesions in F344/N Rats Following Chronic Inhalation Exposure to Naphthalene Vapors

et al. 2003

View full text Add to dashboard Cite

Naphthalene administered by inhalation at concentrations of 10, 30, or 60 ppm for 6 hours per day, 5 days per week for 105 weeks caused nonneoplastic and neoplastic effects in nasal respiratory and olfactory regions of male and female F344/N rats. Non-neoplastic nasal effects were characterized by an increase in the incidence and severity of a complex group of lesions, including atypical hyperplasia, atrophy, chronic inflammation, and hyaline degeneration of olfactory epithelium; hyperplasia, squamous metaplasia, hyaline degeneration, and goblet cell hyperplasia of the respiratory epithelium; and hyperplasia and squamous metaplasia of mucosal glands. Neoplastic effects were characterized by the induction of two types of rare primary nasal tumors, olfactory neuroblastomas and respiratory epithelial adenomas. The incidences of olfactory neuroblastomas in males at 0 ppm, 10 ppm, 30 ppm, and 60 ppm were, respectively, 0%, 0%, 8%, and 6%, whereas in females they were 0%, 4%, 6%, and 24%. The incidences of respiratory epithelial adenomas in males at 0 ppm, 10 ppm, 30 ppm, and 60 ppm were, respectively, 0%, 12%, 17%, and 31% and in females 0%, 0%, 8%, and 4%. The olfactory neuroblastomas and respiratory epithelial adenomas were considered carcinogenic effects related to naphthalene exposure based on their relatively high incidence in exposed rats, their absence in concurrent control rats and NTP historical controls, and their rare spontaneous occurrence in rats of any strain.

show abstract

“…Cytotoxicity data from this study, replotted in Figure 1, indicate that cell killing by both of these naphthalene metabolites is modeled reasonably well as a linear function of log concentration. Note that the relationship shown in Figure 1 predicts the average amount of cell killing observed for cells exposed to 0.1 µg/mL = 0.63 µM 1,4-naphthoquinone, by Sasaki et al, 1997. predicted to be accompanied invariably by substantially increased likelihood of cell death due to cytotoxicity.…”

Section: Correlation Of Genotoxicity and Cytotoxicity Induced By Naphmentioning

confidence: 90%

“…The clearest evidence for this involved human lymphoid cells exposed to 1,2-and/or 1,4-naphthoquinone. After 2 hours of exposure to 0.1 µg/mL (0.63 µM) 1,4-naphthoquinone, MCL-5 human B-lymphocytes (which express several transfected CYP and epoxide hydrolase genes) exhibited a significant (~2-fold) increased frequency of micronuclei, but not of mutation frequency at the TK -or the HPRT -locus assayed (Sasaki et al, 1997). The mutation assay performed was associated with substantially decreased (66 ± 20%) cell survival, but not the micronuclei assay.…”

Section: Correlation Of Genotoxicity and Cytotoxicity Induced By Naphmentioning

confidence: 99%

“…In contrast to the parent compound, naphthalene metabolites, such as 1,2-and 1,4-naphthoquinone, were found to be positive for genotoxicity in a relatively small subset of prokaryotic and eukaryotic in vitro studies involving metabolic activation (Arfsten et al, 1994;Flowers-Geary et al, 1996;NTP, 1992;Wilson et al, 1995Wilson et al, , 1996Sasaki et al, 1997;Yu et al 2002;Schreiner, 2003). The clearest evidence for this involved human lymphoid cells exposed to 1,2-and/or 1,4-naphthoquinone.…”

Section: Correlation Of Genotoxicity and Cytotoxicity Induced By Naphmentioning

confidence: 99%

See 1 more Smart Citation

Mode-of-Action Uncertainty for Dual-Mode Carcinogens: A Bounding Approach for Naphthalene-Induced Nasal Tumors in Rats Based on PBPK and 2-Stage Stochastic Cancer Risk Models

Bogen¹

2007

View full text Add to dashboard Cite

A relatively simple, quantitative approach is proposed to address a specific, important gap in the approach recommended by the USEPA Guidelines for Cancer Risk Assessment to address uncertainty in carcinogenic mode of action of certain chemicals when risk is extrapolated from bioassay data. These Guidelines recognize that some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate "linear" (genotoxic) vs. "nonlinear" (nongenotoxic) approaches to low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient to parameterize a biologically based model that reliably extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach-similar to that used in reference dose procedures for classic toxicity endpoints-can address MOA uncertainty in a way that avoids explicit modeling of low-dose risk as a function of administered or internal dose. Even when a "nonlinear" toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was illustrated for a likely DMOA rodent carcinogen naphthalene, specifically to the issue of risk extrapolation from bioassay data on naphthalene-induced nasal tumors in rats. Bioassay data, supplemental toxicokinetic data, and related physiologically based pharmacokinetic and 2-stage stochastic carcinogenesis modeling results all clearly indicate that naphthalene is a DMOA carcinogen.Plausibility bounds on rat-tumor-type specific DMOA-related uncertainty were obtained using a 2-stage model adapted to reflect the empirical link between genotoxic and cytotoxic effects of the most potent identified genotoxic naphthalene metabolites, 1,2-and 1,4-naphthoquinone.Bound-specific "adjustment" factors were then used to reduce naphthalene risk estimated by linear extrapolation (under the default genotoxic MOA assumption), to account for the DMOA exhibited by this compound.3

show abstract

Genotoxicity induced in human lymphoblasts by atmospheric reaction products of naphthalene and phenanthrene

Cited by 72 publications

References 42 publications

Sources and transformations of particle-bound polycyclic aromatic hydrocarbons in Mexico City

Sources and transformations of particle-bound polycyclic aromatic hydrocarbons in Mexico City

Morphology of Nasal Lesions in F344/N Rats Following Chronic Inhalation Exposure to Naphthalene Vapors

Mode-of-Action Uncertainty for Dual-Mode Carcinogens: A Bounding Approach for Naphthalene-Induced Nasal Tumors in Rats Based on PBPK and 2-Stage Stochastic Cancer Risk Models

Contact Info

Product

Resources

About