title: Life stage-related differences in susceptibility to acrylamide-induced neural and testicular toxicity.
abstract: In order to assess age-dependence of susceptibility to acrylamide (ACR)-induced neural and testicular toxicity, 3- and 7-week-old male SD rats were given ACR at 0, 50, 100, or 200 ppm in the drinking water for 4 weeks, and the nervous and male reproductive systems were examined histopathologically. Testicular genotoxicity was evaluated with the comet assay and the micronucleus (MN) test. Glutathione S-transferase (GST) activity and glutathione (GSH) content in the liver and testis were also measured. In both young and adult animals, neurotoxicity was evident from 100 ppm and increased in proportion to ACR intake per body weight. In the testis, marked degeneration and exfoliation, mainly of spermatids, were observed from 100 ppm limited to young animals. The comet assay revealed ACR to significantly induce DNA damage from 100 ppm in both life stages, while MNs were found only in young rats from 100 ppm. The level of GST activity in the testis of young rats at the end of experiment was significantly lower than that of adult animals, regardless of the ACR treatment. There were no life stage-related differences in GSH contents in the liver and testis. These results suggest that susceptibility to neurotoxicity might not differ between young and adult rats when exposure levels are adjusted for body weight. Regarding testicular toxicity, young animals around puberty proved more susceptible than adult animals, possibly due to their lower level of testicular GST activity than that in adult animals.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Naoki
authors.initials: N
authors.lastname: Koyama
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.forename: Kaoru
authors.initials: K
authors.lastname: Irie
authors.forename: Tomomi
authors.initials: T
authors.lastname: Morikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Honma
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology; D020552:Comet Assay; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000473:pathology
chemical_list: D020106:Acrylamide; D005982:Glutathione Transferase; D005978:Glutathione