Species-specific testicular and hepatic microsomal metabolism of benzo(a)pyrene, an ubiquitous toxicant and endocrine disruptor

Smith, Tené L.; Merry, Shayla T.; Harris, Deacqunita L.; Ford, J. J.; Ike, Justus; Archibong, Anthony E.; Ramesh, Aramandla

doi:10.1016/j.tiv.2007.01.005

Cited by 36 publications

(13 citation statements)

References 30 publications

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“…The FLA and BaP metabolite types identified in our study are in accord with published literature, which used microsomes from intestinal, hepatic and extra-hepatic tissues (Walker et al, 2006; Smith et al, 2007; Harris et al, 2009b). However, the variation in proportion of specific BaP/FLA metabolic types generated from the adipose microsomes could be attributed to the competition for microsomal metabolizing enzymes and the relative stability of the metabolites of one compound versus the other.…”

Section: Discussionsupporting

confidence: 84%

Effect of benzo(a)pyrene exposure on fluoranthene metabolism by mouse adipose tissue microsomes

Huderson

Harris

Niaz

et al. 2010

Toxicology Mechanisms and Methods

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The present study has been undertaken to examine whether exposure to benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound influences the metabolism of fluoranthene (FLA), another PAH compound. Microsomes were isolated from the adipose tissue of mice that received 50 μg/kg BaP and incubated with FLA (3μM) alone; FLA in combination with BaP at equimolar concentrations and a control group that received nothing. Post-incubation, samples were extracted with ethyl acetate and analyzed for FLA metabolites by reverse-phase HPLC with fluorescence detection. The rate of FLA metabolism (pmol of metabolite/min/mg protein) was increased when microsomes from BaP-treated mice were exposed to FLA alone and FLA in combination with BaP, compared to controls. On the other hand, the difference in FLA metabolic rate between microsomes that were exposed to FLA + BaP was higher than the ones that received FLA. The microsomes from BaP-pretreated mice produced considerably higher proportion of FLA 2, 3-diol, and 2, 3 D FLA when microsomes were incubated with FLA. There were no differences in the FLA metabolite types formed when BaP-pretreated mice were co-incubated with BaP and FLA, than FLA alone. The enhanced biotransformation of FLA as a result of prior and concomitant exposure to BaP may have implications for assessment of risks arising from human exposure to PAH mixtures.

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Section: Discussionsupporting

confidence: 84%

Effect of benzo(a)pyrene exposure on fluoranthene metabolism by mouse adipose tissue microsomes

Huderson

Harris

Niaz

et al. 2010

Toxicology Mechanisms and Methods

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“…The prostate may be most susceptible to endogenous hormone exposure during puberty [45,46], when it rapidly undergoes differentiation and maturation [47]. Smoking is also related to earlier puberty onset [48][49][50], and earlier puberty may be a risk factor for prostate cancer [45,51]. Age at smoking initiation has not been previously reported in prospective studies [9].…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoking and risk of prostate cancer among Singapore Chinese

Butler

Wang

Wong

et al. 2009

Cancer Causes Control

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Prospective epidemiologic studies conducted in Western populations support an association between current smoking and aggressive subtypes of prostate cancer. In Singapore, where prostate-specific antigen is not used for population-wide screening, prostate cancer incidence has tripled within the past two decades. Using Cox regression methods, we examined the relationship between smoking and prostate cancer established between 1993 and 1998 in a cohort of 27,293 Singapore Chinese men. As of December 2006, 250 incident prostate cancer cases were diagnosed. In our cohort, 42.2% reported never smoking cigarettes, 15.7% quit over 5 years ago (long-term former), 5.7% quit within the past 5 years (recent former), and 36.4% were current smokers. From multivariable models, we observed no association with smoking status, age at starting to smoke, years smoked, or number of cigarettes per day. Among recent former and current smokers combined, we observed a small positive association for earlier age at starting to smoke that was somewhat stronger for nonadvanced disease (hazard ratio = 1.63, 95% confidence interval: 0.85, 3.12, for <15 years versus nonsmokers). Smoking was not a major risk factor for prostate cancer in our Singapore Chinese cohort, a traditionally low risk population with parallel increases in incidence and mortality.

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“…Benzo[ a ]pyrene (BaP), which belongs to the polycyclic aromatic hydrocarbons family (PAHs), has been confirmed to be a procarcinogen by the International Agency for Research on Cancer (IARC, ). It is also generally believed to induce male reproductive toxicity (Jeng, Yordt, Davis, & Swanson, ; Smith et al, ). BaP is a widespread harmful substance found in food, coal tar, industrial smoke and cigarette smoke (Callén, López, Iturmendi, & Mastral, ; Wang et al, ).…”

Section: Introductionmentioning

confidence: 99%

Benzo[a]pyrene‐decreased gap junctional intercellular communication via calcium/calmodulin signaling increases apoptosis in TM4 cells

Chou

et al. 2018

J of Applied Toxicology

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The mechanism of male reproductive toxicity induced by benzo[a]pyrene (BaP) is poorly understood. Gap junctional intercellular communication (GJIC) is known to play a critical role in maintaining spermatogenesis. The aim of the present study was to determine the toxic effects of BaP in Sertoli cells, and to explore the possibility and potential mechanisms of BaP-induced changes in the level of GJIC, and the relationship between GJIC and BaP-induced apoptosis. We treated mouse Sertoli cell lines (TM4) with different concentrations (0.1-100 μm) of BaP for 1-48 hours, and found that GJIC exhibited a dose- and time-dependent downregulation. Treatment with 10 μm BaP increased apoptosis, intracellular Ca level ([Ca ] ) and calmodulin (CaM) protein expression, and decreased the protein level of connexin 43 (Cx43) (also known as gap junction α-1 protein [GJA1]) in TM4 cells. However, BaP had no effect on the phosphorylation of Cx43 at Ser279/282, Ser255, Ser368 or Ser262. Downregulation of [Ca ] by BAPTA-AM significantly attenuated the BaP-induced GJIC suppression, Cx43 protein decrease and CaM protein increase. Interestingly, inhibition of CaM expression by W7 partially recovered BaP-induced GJIC inhibition, but had no effect on BaP-induced Cx43 protein decrease. Pretreatment with the GJIC activator retinoic acid significantly mitigated BaP-induced apoptosis. In conclusion, these results suggest that BaP can decrease GJIC via Ca /CaM signaling, and that BaP-induced GJIC suppression increases apoptosis in TM4 cells.

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Species-specific testicular and hepatic microsomal metabolism of benzo(a)pyrene, an ubiquitous toxicant and endocrine disruptor

Cited by 36 publications

References 30 publications

Effect of benzo(a)pyrene exposure on fluoranthene metabolism by mouse adipose tissue microsomes

Effect of benzo(a)pyrene exposure on fluoranthene metabolism by mouse adipose tissue microsomes

Cigarette smoking and risk of prostate cancer among Singapore Chinese

Benzo[a]pyrene‐decreased gap junctional intercellular communication via calcium/calmodulin signaling increases apoptosis in TM4 cells

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