Pharmacokinetics of low doses of benzo[a]pyrene in the rat

Foth, Heidi; Kahl, Regine; Kahl, Georg F.

doi:10.1016/0278-6915(88)90040-3

Cited by 62 publications

(42 citation statements)

References 11 publications

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“…Although the oral bioavailability of B[a]P is thought to be low (Foth et al, 1988), studies have demonstrated that B[a]P is rapidly absorbed in the epithelial cells but is slowly transported into the adjacent capillary bed (Plant et al, 1987). Thus, the epithelium may accumulate high concentrations even at low environmental exposure levels, and long colonic and intracellular residence times may lead to substantial local metabolic activation, even when enzymatic activity is low (Gerde et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Specific Antibody Modulates Absorptive Transport and Metabolic Activation of Benzo[a]pyrene across Caco-2 Monolayers

Buck¹,

Augustijns²

2005

J Pharmacol Exp Ther

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It has been shown that oral anticarcinogen antibodies can decrease intestinal absorption of procarcinogens. So far, no attempts have been made to understand the potential modulatory effect of such antibodies on metabolic activation at mucosal surfaces. Moreover, the influence of naturally induced serosal-specific antibodies on absorptive transport of carcinogens remains unknown. In this study, the prototype food carcinogen benzo[a]pyrene (B[a]P) and a specific monoclonal antibody were used to address these questions in a bicompartmental model of polarized intestinal cells (Caco-2). Apical (i.e., luminal) administration of a 30-fold molar excess antibodies increased about 25-fold recovery of unmetabolized B[a]P, concomitantly with a decrease of 80% in both absorptive transport and formation of phenol metabolites. Interestingly, when metabolism was slowed down by antibodies, cross-reactive antibodies also increased at least 5-fold the extracellular levels of the 7,8-diol-B[a]P, interrupting subsequent activation steps. On the other hand, basolateral antibodies changed by 8-fold the rate of carcinogen appearance in the basolateral compartment, albeit without interfering with the apical cellular uptake or sequestration of either B[a]P or 7,8-diol-B[a]P by apical antibodies. Furthermore, basolateral antibodies reduced exposure of Caco-2 monolayers to B[a]P as demonstrated by a 50% decrease in apical efflux of 3-OH-B[a]P. These data show for the first time that both luminal and serosal antibodies may reduce the carcinogenic process by preventing high local concentrations, which would overload DNA repair mechanisms. This study also sheds light on the relevance of both naturally induced and immunoprophylactic antibodies against polycyclic aromatic hydrocarbon carcinogens.

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Section: Discussionmentioning

confidence: 99%

Specific Antibody Modulates Absorptive Transport and Metabolic Activation of Benzo[a]pyrene across Caco-2 Monolayers

Buck¹,

Augustijns²

2005

J Pharmacol Exp Ther

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“…The half-life of nicotine in the rat is only about 1 h (Kyerematen et al, 1988), so it is highly unlikely that the effects of premating TSE exposure reflect this chemical component. However, the same is not true for nicotine metabolites that are also potentially bioactive, and which have half-lives of several days (Kyerematen et al, 1988), or for potentially long-lived lipophilic organic chemicals in TSE; for example, the terminal half-life of benzo [a]pyrene is about 17 hr (Foth et al, 1988). A second possibility is that TSE could produce lasting changes in maternal physiology, hormonal status and/or placental formation or function.…”

Section: Discussionmentioning

confidence: 99%

Is There a Critical Period for the Developmental Neurotoxicity of Low-Level Tobacco Smoke Exposure?

Slotkin¹,

Stadler²,

Skavicus³

et al. 2016

Toxicol. Sci.

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Secondhand tobacco smoke exposure in pregnancy increases the risk of neurodevelopmental disorders. We evaluated in rats whether there is a critical period during which tobacco smoke extract (TSE) affects the development of acetylcholine and serotonin systems, prominent targets for adverse effects of nicotine and tobacco smoke. We simulated secondhand smoke exposure by administering TSE so as to produce nicotine concentrations one-tenth those in active smoking, with 3 distinct, 10-day windows: premating, early gestation or late gestation. We conducted longitudinal evaluations in multiple brain regions, starting in early adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure in any of the 3 windows impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although the adverse effects were seen for all 3 treatment windows, there was a distinct progression, with lowest sensitivity for premating exposure and higher sensitivity for gestational exposures. Serotonin receptors were also reduced by TSE exposure with the same profile: little effect with premating exposure, intermediate effect with early gestational exposure and large effect with late gestational exposure. As serotonergic circuits can offset the neurobehavioral impact of cholinergic deficits, these receptor changes were maladaptive. Thus, there is no single 'critical period' for effects of low-level tobacco smoke but there is differential sensitivity dependent upon the developmental stage at the time of exposure. Our findings reinforce the need to avoid secondhand smoke exposure not only during pregnancy, but also in the period prior to conception, or generally for women of childbearing age.

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“…Based on a EPA model (EPA, 1989) for particle bound chemicals, the inhalatory pyrene intake was estimated under the assumption that about 25% of inspired particles are exhaled, 12.5% are deposited in the lower respiratory tract and 62.5% are eliminated from the lungs and swallowed. Furthermore it was assumed that the elution of pyrene from the deposited particles in the lower respiratory tract is 100%, and that of the swallowed fraction of the particle bound pyrene, 40% is absorbed in the gastrointestinal tract (Forth et al, 1988). An absorption factor of 70% of gaseous pyrene was used.…”

Section: Toxicokineticsmentioning

confidence: 99%

Airborne exposure to polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene of carbon anode plant workers

Petry

Schmid

Schlatter

1996

The Annals of Occupational Hygiene

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Abstract-(Workers in plants producing carbon anodes for aluminium electrolysis are exposed to PAHs containing coal tar pitch volatiles, pitch and coke. The aim of this study was to evaluate the suitability of urinary 1-hydroxypyrene to characterize respiratory exposure to PAH, which is most relevant for assessing individual health risks. Six workers in a carbon anode plant volunteered to take part in a personal air sampling and a biological monitoring programme lasting five consecutive 8-h shifts to determine occupational exposure to airborne PAHs and urinary excretion of 1-hydroxypyrene. Exposure to total PAH for all worksites varied from 3.99 to 120.6 ug PAH m"* and for benzo(a)pyrene (BaP) from 0.17 to 4.88 /ig BaP m~3. The concentration of 1-hydroxypyrene in post-and pre-shift urine samples was in the range (0.5-61.8 iano\ 1-OHP per mol creatinine) and depended on the worksite. The Spearman rank correlation test showed a low but significant (P<0.05) correlation of urinary 1-hydroxypyrene in the post-and pre-shift samples with respiratory pyrene exposure. The quantitative aspects of biological monitoring for the evaluation of respiratory PAH exposure were tested with a pharmflcokinetic model. On the basis of individual pyrene exposure, excretion of urinary 1-hydroxypyrene during the working week was calculated for each worker. The results presented in this investigation indicate that biological monitoring of the pyrene metabolite 1-hydroxypyrene is a useful indicator of a general PAH exposure, but cannot replace personal air sampling for assessing the lung cancer risk of individuals^

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Pharmacokinetics of low doses of benzo[a]pyrene in the rat

Cited by 62 publications

References 11 publications

Specific Antibody Modulates Absorptive Transport and Metabolic Activation of Benzo[a]pyrene across Caco-2 Monolayers

Specific Antibody Modulates Absorptive Transport and Metabolic Activation of Benzo[a]pyrene across Caco-2 Monolayers

Is There a Critical Period for the Developmental Neurotoxicity of Low-Level Tobacco Smoke Exposure?

Airborne exposure to polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene of carbon anode plant workers

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