Regular articleMechanisms by which benzo[a]pyrene, an environmental carcinogen, suppresses B cell lymphopoiesis
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2013, Toxicology and Applied PharmacologyCitation Excerpt :Since environmental or occupational exposure to B[a]P is associated with diseases only after long-term exposure, most animal experimental models use high concentrations of B[a]P to obtain a short-term readout. However, these high concentrations are not representative of environmental exposure and can normally not be matched by equimolar concentrations of antibodies obtained after active immunization (Hardin et al., 1992). One of the most important challenges of the immunoprophylactic strategy against B[a]P is the necessity to develop in vivo models based on low concentrations of B[a]P that can be matched by excess molar concentrations of antibody and that give measurable surrogate read-outs in short-term or long-term experiments.
Evaluation of probable specific immunotoxic effects of cigarette smoking in smokers
2013, Egyptian Journal of Forensic SciencesCitation Excerpt :However, the mechanism by which cigarette smoke changes in the immune response remains poorly understood.4 Smoking may depress immune function because nicotine stimulates the hypothalamic-pituitary-adrenal axis15 thereby elevating levels of endogenous glucocorticoids, which are powerful immunosuppressants in vivo16 and in vitro17 finally, tobacco-related polycyclic aromatic hydrocarbons, such as benzo{a}pyrene, have been implicated in the suppression of B-cell lymphopoiesis and cytotoxicity in lymphokine-activated killer cells.18 In a major study of lifestyle factors and health involving 2892 Japanese men and women, cigarette smoking was associated with decreased Natural killer cytotoxic activity however, immune system functioning is influenced by other lifestyle variables, such as diet, alcohol consumption, daily workload, sleep, body weight and psychological stress19 thus an improvement in immune function after smoking cessation could result from other lifestyle changes, which accompany smoking cessation.
7,12-Dimethylbenzanthracene induces apoptosis in RL95-2 human endometrial cancer cells: Ligand-selective activation of cytochrome P450 1B1
2012, Toxicology and Applied PharmacologyCitation Excerpt :In addition, DMBA is immunosuppressive and has been shown to cause a severe loss of bone marrow cellularity (Ward et al., 1984). It has been suggested that DMBA-induced bone marrow cytotoxicity is a consequence of apoptosis in developing leukocytes (Hardin et al., 1992; Yamaguchi et al., 1997). DMBA, like other PAHs, requires transformation by cytochrome P450 (CYP) and microsomal epoxide hydrolase (mEH) in order to express its carcinogenicity; its 3,4-diol derivative is thought to be a procarcinogen that is further modified by CYP to produce the ultimate carcinogen, 1,2-epoxide-3,4-diol-DMBA (DMBA-DE), which binds to DNA (Cheng et al., 1988a).