Circadian rhythm of covalent modifications in liver DNA.
32P-postlabeling analysis recently revealed that in addition to 5-methylcytosine, mammalian DNA contains covalently modified nucleotides of unknown structures and functions termed I-compounds whose levels increase with age. I-compound levels, in addition, depend on species, strain, sex, tissue, and diet and are generally lowered by carcinogen exposure. As shown here, levels of several non-polar I-compounds in liver DNA of untreated male C3H mice were elevated 2 to 8.5 times at 1800 h and 2400 h as compared to 0600 h and 1200 h, while polar I-compounds and persistent carcinogen-DNA adducts induced by safrole were unaffected by time of day. In liver DNA of male F-344 rats 4 non-polar I-compounds and 4 polar I-compounds showed significant circadian rhythm at 2000 h compared to 0800 h. This novel circadian variation of DNA structure implies mechanisms precisely regulating I-compound levels in vivo and may conceivably be linked to diurnal differences of DNA synthesis and gene expression.
Nath
R G
RG
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Vulimiri
S V
SV
Randerath
K
K
D000818:Animals; D001345:Autoradiography; D002273:Carcinogens / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D002940:Circadian Rhythm; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010761:Phosphorus Radioisotopes; D051381:Rats; D011916:Rats, Inbred F344; D012451:Safrole / Q000494:pharmacology
D002273:Carcinogens; D010761:Phosphorus Radioisotopes; D004247:DNA; D012451:Safrole