Acrylamide, an in vivo thyroid carcinogenic agent, induces DNA damage in rat thyroid cell lines and primary cultures.
Chronic treatment of rats with acrylamide induces various tumors among which thyroid tumors are the most frequent. The aim of the present study was to develop an in vitro model of acrylamide action on thyroid cells to allow the investigation of the mechanism of this tumorigenic action. The first part of the study considered as targets, characteristics of thyroid metabolism, which could explain the thyroid specificity of acrylamide action: the cAMP mitogenic effect and the important H2O2 generation by thyroid cells. However, acrylamide did not modulate H2O2 or cAMP generation in the thyroid cell models studied. No effect on thyroid cell proliferation was observed in the rat thyroid cell line FRTL5. On the other hand, as shown by the comet assay, acrylamide induced DNA damage, as the positive control H2O2 in the PC Cl3 and FRTL5 rat thyroid cell lines, as well as in thyroid cell primary cultures. The absence of effect of acrylamide on H2AX histone phosphorylation suggests that this effect does not reflect the induction of DNA double strand breaks. DNA damage leads to the generation of mutations. It is proposed that such mutations could play a role in the carcinogenic effect of acrylamide. The mechanism of this effect can now be studied in this in vitro model.
Chico Galdo
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Institute of Interdisciplinary Research (IRIBHM), Université Libre de Bruxelles, Campus Erasme CP602, 808 Route de Lennik, B-1070 Brussels, Belgium.
Massart
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C
Jin
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L
Vanvooren
V
V
Caillet-Fauquet
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P
Andry
G
G
Lothaire
P
P
Dequanter
D
D
Friedman
M
M
Van Sande
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J
D020106:Acrylamide / Q000633:toxicity*; D018263:Adenocarcinoma, Follicular / Q000139:chemically induced; D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D018929:Cell Culture Techniques; D002460:Cell Line; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D020552:Comet Assay / Q000379:methods; D000242:Cyclic AMP / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D051381:Rats; D012756:Sheep; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects*; D013964:Thyroid Neoplasms / Q000139:chemically induced*; D013972:Thyrotropin / Q000494:pharmacology
D004852:Epoxy Compounds; D005576:Colforsin; D020106:Acrylamide; C071834:glycidamide; D013972:Thyrotropin; D006861:Hydrogen Peroxide; D000242:Cyclic AMP