3-Methylcholanthrene induces lymphocyte and phagocyte apoptosis in common carp (Cyprinus carpio L) in vitro.
Polycyclic aromatic hydrocarbons (PAH) are an important class of environmental pollutant that are known to be carcinogenic and immunotoxic. In mammals it was suggested that PAH compromise the immune system in part through the induction of programed cell death (apoptosis). In fish, no study has reported the importance of this physiological process in PAH-induced immunotoxicity. We have therefore investigated the capacity of 3-methylcholanthrene to induce lymphocyte and phagocyte apoptosis in carp. By three criteria (exposition of phosphatidylserine at the outer cell membrane, chromatin condensation and fragmentation, and decreased cell size) the data indicate that 3-methylcholanthrene (3-MC) treatment (from 20 to 200 microM) during 24 h produces apoptosis in both lymphocytes and phagocytes. In order to evaluate whether 3-MC induced apoptosis is related to the metabolic activation of 3-MC or 3-MC Ah-R binding, co-exposure experiments with 3-MC and alpha-naphtoflavone (alpha-NF), a compound that inhibits metabolic activation of 3-MC and 3-MC Ah-R binding were performed. While alpha-NF did not prevent 3-MC-induced apoptosis, the compound itself was found to be a strong inducer of apoptosis. There results might indicate that metabolic activation of 3-MC or 3-MC Ah-R binding is not causally linked to apoptosis. However, since 3-MC, alpha-NF and 3-MC + alpha-NF treatments produce the same sustained increase (3 h minimum) in intracellular calcium level, it is possible that this phenomenon is implicated in the induction of programmed cell death by these hydrocarbons.
Reynaud
S
S
Laboratory of General and Comparative Immunophysiology, Teaching and Research Unity of Sciences, 123, Av. Albert Thomas, 87060 Limoges, France. steph.reynaud@caramail.com
Duchiron
C
C
Deschaux
P
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001551:Benz(a)Anthracenes / Q000633:toxicity; D001571:Benzoflavones / Q000378:metabolism; D002118:Calcium; D002347:Carps / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects; D005434:Flow Cytometry; D008214:Lymphocytes / Q000187:drug effects*; D008748:Methylcholanthrene / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D010586:Phagocytes / Q000187:drug effects*; D010718:Phosphatidylserines / Q000378:metabolism; D023382:Toxicity Tests, Acute; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D001551:Benz(a)Anthracenes; D001571:Benzoflavones; D002843:Chromatin; D010718:Phosphatidylserines; D014874:Water Pollutants, Chemical; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D002118:Calcium