Tumorigenic activity of non-alternant polynuclear aromatic hydrocarbons in newborn mice

LaVoie, Edmond J.; Braley, Joanne; Rice, Joseph E.; Rivenson, Abraham

doi:10.1016/0304-3835(87)90068-1

Cited by 30 publications

(13 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, significantly lower amounts of metabolites were detected in the feces and urine of females relative to males following oral exposure (Van de Wiel et al, 1993). This sex-specific difference in BaP metabolism (albeit reported only in rats, to the best of our knowledge) may contribute to the greater incidence of BaP-induced liver (Lavoie et al, 1987; Wislocki et al, 1986) and lung (Lavoie et al, 1987) tumors in male rodents. In general, the very short half-life of BaP in rats (about 1, 4 and 6 hours for oral, dermal and inhalation exposures, respectively [Carlson et al, 1986; Ramesh et al, 2002], and approximately 2–5 hours in mouse blood after oral administration [Uno et al, 2006]) suggests that BaP is rapidly metabolized and excreted.…”

Section: Traditional Risk Assessment Approach (Ra1)mentioning

confidence: 77%

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Moffat

Chepelev

Labib

et al. 2015

Critical Reviews in Toxicology

138

100

View full text Add to dashboard Cite

Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lung 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work.

show abstract

Section: Traditional Risk Assessment Approach (Ra1)mentioning

confidence: 77%

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Moffat

Chepelev

Labib

et al. 2015

Critical Reviews in Toxicology

138

100

View full text Add to dashboard Cite

show abstract

“…In addition, B(a)P has induced cancer in many of these animal tissues (Jerina et al, 1980;Lavoie et al, 1987;Iwagawa and Maeda, 1992;Likhachev et al, 1992). Epidemiological studies have reported increased incidences of lung and skin cancers in humans occupationally exposed to B(a)P (Lloyd, 1971;Hammond et al, 1976;Redmond et al, 1976;Jerina et al, 1980;Maclure and MacMahon, 1980).…”

Section: Introductionmentioning

confidence: 93%

“…Induction of CYPIA1 is relevant to human health because B(a)P requires metabolic activation to 7,8-diol-9,10-epoxide before eliciting many of its toxic effects (Sutter and Greenlee, 1992;Eaton, 1995;Salas and Burchiel, 1998;Nebert et al, 2000). The 7,8-diol-9,10-epoxide metabolite is believed to be responsible for carcinogenicity, teratogenicity, immune and developmental toxicity in rats (Redmond et al, 1976;Maclure and MacMahon, 1980;Lavoie et al, 1987;Eaton, 1995;Salas and Burchiel, 1998). Levels of activating enzymes, however, are not the sole determinants of B(a)P toxicity; sufficient quantities of detoxifying enzymes are also critical.…”

Section: Introductionmentioning

confidence: 98%

Behavioral effects induced by acute exposure to benzo(a)pyrene in F-344 rats

2001

View full text Add to dashboard Cite

Polycyclic aromatic hydrocarbons (PAHs) are highly persistent environmental pollutants which pose potential adverse effects on human health. Benzo(a)-pyrene (B(a)P) is the prototypical representative of these widely dispersed lipophylic contaminants. (B(a)P) exposure in experimental animals results in an array of tissue- and organ-specific responses including carcinogenicity, teratogenicity, reproductive and immunotoxicity. However, no previous studies have examined the potential neurobehavioral toxicity of B(a)P in vivo. The present study was conducted to investigate the behavioral effects induced by single oral doses of (B(a)P) in 8-week-old male and female F-344 rats. Rats were exposed to 0, 12.5, 25, 50, 100 and 200 mg/kg of B(a)P by oral gavage. Motor activity measurements and the functional observational battery (FOB) were used to assess behavioral changes induced by B(a)P at 2, 4, 6, 8, 10, 12, 24, 48, 72 and 96 h post treatment. Statistical analyses revealed significant (p <0.001) dose, sex and time interactions. (B(a)P) doses ranging from 25 to 200 mg/kg produced a significant suppression (up to 60%) in four motor activity parameters: horizontal activity, total distance, stereotype and vertical activity in both sexes within 2 and 4h of dosing. B(a)P treated male and female animals also showed significant (p <0.001) changes in neuromuscular, autonomic, sensorimotor and physiological functions within 2 and 4h post B(a)P administration except in the 12.5 mg/kg treatment group. The 12.5 mg/kg dose did not produce significant (p > 0.05) behavioral toxicity in either males or females. All treated animals (25-200 mg/kg) recovered from the toxic effects of B(a)P by 72 h. Significant (p < 0.05) gender differences were noted in FOB test measures with males displaying greater sensitivity to B(a)P. These data suggest that motor activity and FOB measurements can be used as indices to detect B(a)P neurotoxicity.

show abstract

“…In all of these studies, benzo[b]-fluoranthene exhibited a significant carcinogenic activity. (110,111,119,120), by intraperitoneal injection into newborn mice in two studies (114,121) and by intrapulmonary implantation into rats in one study (114 (122), intraperitoneal injection into newborn mice in one study (114), and intrapulmonary implantation into rats in one study (118 …”

Section: Workplace Methodsmentioning

confidence: 99%

“…(107)(108)(109)(110)(111)(112)(113), intraperitoneal injection into mice in multiple studies (106,(114)(115)(116)(117), and intrapulmonary implantation into rats in one study (118). In all of these studies, benzo[b]-fluoranthene exhibited a significant carcinogenic activity.…”

Section: Workplace Methodsmentioning

confidence: 99%

Polycyclic Aromatic Hydrocarbons and Azaaromatic Compounds

Baxter¹,

Warshawsky²

2012

Patty's Toxicology

View full text Add to dashboard Cite

Polycyclic aromatic hydrocarbons (PAHs) are moderately reactive, but undergo photochemical degradation in the atmosphere, and are widely used as chemical raw materials. Aromatic hydrocarbons cause local irritation and changes in endothelial cell permeability and are absorbed rapidly. Accumulation of aromatic hydrocarbons in marine animals occurs to a greater extent and retention is longer compared to alkanes. Toxicity of polynuclear aromatics has been reported comprehensively. It has been reported that exposure to a variety of complex mixtures containing these chemicals, such as soot, coal tar and pitch, mineral oils, coal gasification residues, and cigarette smoke has historically been associated with induction of cancer. Naphthalene causes cataracts in the eyes of experimental animals. Its vapors may cause severe systemic injury. Alkylbenzenes are readily aspirated and produce instant death via cardiac arrest and respiratory paralysis. In general, the acute toxicity of alkylbenzenes is higher for toluene than that for benzene and decreases further with increasing chain length of the substituent, except for highly branched C 8 to C 18 derivatives. Polycyclic aromatic hydrocarbons are metabolized through epoxides and hydroxides and are excreted as conjugates.

show abstract

Tumorigenic activity of non-alternant polynuclear aromatic hydrocarbons in newborn mice

Cited by 30 publications

References 7 publications

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Behavioral effects induced by acute exposure to benzo(a)pyrene in F-344 rats

Polycyclic Aromatic Hydrocarbons and Azaaromatic Compounds

Contact Info

Product

Resources

About