Physicochemical alterations in the conformation of rat liver chromatin induced by carcinogens in vivo.
Administration of methylating carcinogens such as methyl methanesulfonate (120 mg/kg), dimethylnitrosamine (5 mg/kg), or methylnitrosourea (80 mg/kg) to rats resulted in an increased ellipticity in circular dichroism spectra and in an enhanced ability to bind ethidium bromide in the liver chromatin. Although shearing of the chromatin preparations increased both the ellipticity and number of binding sites for ethidium bromide, the carcinogen-induced effects were noticeable whether or not chromatin was sheared. Although the doses of the 3 carcinogens used in these studies are equivalent in their ability to induce strand breaks in liver DNA at 4 hr, their effects on the induction of conformational changes in liver chromatin are different. For example, methyl methanesulfonate induced the minimum conformational changes in liver chromatin at 4 hr, whereas methylnitrosourea induced the maximum changes at 4 hr. Methyl methanesulfonate and dimethylnitrosamine, on the other hand, induced maximum changes at 3 days. The conformational changes induced by methyl methanesulfonate and methylnitrosourea, and not by dimethylnitrosamine, tend to be repaired by 14 days.
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002843:Chromatin / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D002942:Circular Dichroism; D004247:DNA / Q000032:analysis; D004260:DNA Repair; D004128:Dimethylnitrosamine / Q000494:pharmacology; D004996:Ethidium / Q000378:metabolism; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000032:analysis; D051381:Rats; D013997:Time Factors
D002273:Carcinogens; D002843:Chromatin; D011506:Proteins; D012313:RNA; D008770:Methylnitrosourea; D004247:DNA; D008741:Methyl Methanesulfonate; D004996:Ethidium; D004128:Dimethylnitrosamine