Methylcholanthrene causes increased thymocyte apoptosis.
The polycyclic aromatic hydrocarbon (PAH), methylcholanthrene (MCA), is a well studied carcinogen and a teratogen. MCA and other PAH cause immune suppression of B cell and T cell responses in mice and MCA had been reported to induce thymus atrophy. Here we show that MCA treatment causes thymus atrophy in adrenalectomized mice and in C57BL/6 and DBA/2 mice which differ in aryl hydrocarbon receptor (AhR) expression. This indicates that MCA-mediated thymus atrophy is mediated, at least in part, by glucocorticoid hormone receptor- and aryl hydrocarbon receptor-independent mechanisms. Assay of thymocytes, both in situ and ex vivo, demonstrate that MCA induces thymocyte apoptosis. Apoptotic thymocytes can be found within or adjacent to thymic Mphi, suggesting rapid phagocytosis. Mice that are deficient in tumor necrosis factor-alpha receptor-1 or p53, or that overexpress bcl-2 are susceptible to MCA-mediated thymus atrophy.
Lutz
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CT
Department of Pathology, University of Iowa, Iowa City 52242, USA. charles-lutz@uiowa.edu
Browne
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Petzold
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CR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005821:Genetic Techniques; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000187:drug effects; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis* / Q000187:drug effects; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure
D002273:Carcinogens; D018336:Receptors, Aryl Hydrocarbon; D008748:Methylcholanthrene; D004247:DNA