Subchronic acrylamide treatment induces a tissue-specific increase in DNA synthesis in the rat.
Chronic treatment with acrylamide results in increased incidence of adrenal (pheochromocytoma), testicular (mesotheliomas) and thyroid (adenoma) neoplasia in male rats. While acrylamide has been demonstrated to be DNA reactive, the tissue pattern of neoplasm induction by acrylamide suggests other mechanisms in addition to DNA reactivity may be involved in the carcinogenesis of this compound. The present studies were performed to determine whether acrylamide or an acrylamide metabolite altered cell growth in the neoplastic target tissues in the rat. DNA synthesis, mitosis and apoptosis were examined in F344 and Sprague-Dawley male rats treated with acrylamide (0, 2, or 15 mg/kg/day) for 7, 14, or 28 days. Acrylamide increased DNA synthesis in the target tissues for tumor development (thyroid, testicular mesothelium, adrenal medulla) in both rat species. In contrast, cell growth was not altered in the liver and adrenal cortex (non-target tissues for acrylamide carcinogenesis). No changes in apoptosis or mitosis were observed in any of the tissues examined. Inhibition of oxidative metabolism of acrylamide using 1-aminobenzotriazole reduced acrylamide-induced DNA synthesis only in the adrenal medulla, having no apparent effect in the testicular mesolthelium or thyroid. In summary, acrylamide produced a selective increase in DNA synthesis that correlates with the previously reported tumor target tissues.
Lafferty
Jeffery S
JS
Division of Toxicology, Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, 635 Barnhill Dr., MS 551, Indianapolis, IN 46202, USA.
Kamendulis
Lisa M
LM
Kaster
JuLee
J
Jiang
Jiazhong
J
Klaunig
James E
JE
D020106:Acrylamide / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008938:Mitosis / Q000187:drug effects; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology
D004785:Environmental Pollutants; D014230:Triazoles; C033020:1-aminobenzotriazole; D020106:Acrylamide; D004247:DNA; D001973:Bromodeoxyuridine