Effects of the antioxidant butylated hydroxytoluene (BHT) on retinal degeneration induced transplacentally by a single low dosage of N-methyl-N-nitrosourea (MNU).
A 1 mg/kg dose of the DNA alkylating agent, N-methyl-N-nitrosourea (MNU), when administered on day 16 of gestation provokes a progressive retinal degeneration in CD-1 albino mice reared under standard fluorescent lighting conditions (12 hr light: 12 hr dark); this degeneration begins at about 4 weeks post-natally and worsens with age. It is accelerated by constant fluorescent light exposure but is retarded greatly by constant darkness, suggesting the importance of secondary insults in the post-natal period for development of the degenerative disease. To determine whether the secondary photochemical damage might be specifically blocked, MNU-exposed and control animals in the present study were fed an antioxidant-enriched diet of Purina mouse chow supplemented with 0.75% butylated hydroxytoluene (BHT). A second group of MNU-exposed and control animals were fed a non-BHT supplemented standard Purina mouse chow diet. Systematic measurements of the number of rows of photoreceptor cell nuclei, the thickness of the inner/outer segment layer, and the thickness of the whole retina were made, to quantify and degenerative changes in animals 2, 4, 6, and 8 weeks of age. By 8 weeks, retinas of BHT-fed, MNU-exposed animals were significantly thicker and had more rows of photoreceptor cell nuclei than regular-diet, MNU-exposed animals. Moreover, the retinas of BHT-fed animals, both for MNU-exposed and controls, demonstrated sporadic morphologic changes in the form of circular configurations composed of ganglion cells, arcades of nuclear and plexiform layers, and, in one control animal, a hyperplastic nodule. These experiments suggested that MNU-induced retinal degeneration may be retarded by a BHT-enriched diet; however, continuous high doses of this compound pre- and postnatally may induce other retinal abnormalities.
Smith
S B
SB
Department of Anatomy, University of South Alabama, College of Medicine, Mobile.
Cooke
C B
CB
Yielding
K L
KL
D000818:Animals; D000975:Antioxidants; D002084:Butylated Hydroxytoluene / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000648:ultrastructure; D005260:Female; D008431:Maternal-Fetal Exchange; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D010786:Photoreceptor Cells / Q000166:cytology; D011247:Pregnancy; D012016:Reference Values; D012160:Retina / Q000166:cytology / Q000473:pathology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000196:embryology* / Q000517:prevention & control; D013723:Teratogens
D000975:Antioxidants; D013723:Teratogens; D002084:Butylated Hydroxytoluene; D008770:Methylnitrosourea