Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1987-7-23
pubmed:abstractText
A new viscometric technique, capable of detecting DNA strand breaks and alkali-labile sites by monitoring time-dependent changes of DNA-reduced viscosity, has been used to analyze dose-response curves for the induction of DNA damage in liver of rats treated with single p.o. doses of sixteen N-nitroso compounds. Statistically significant changes of DNA viscometric parameters, which are considered indicative of DNA fragmentation, were produced by N-nitrosodimethylamine (0.022 mg/kg), N-nitrosomethylethylamine (0.025 mg/kg), N-nitrosodiethylamine (0.067 mg/kg), N-nitrosodiethanolamine (1.03 mg/kg), N-nitrosodi-n-propylamine (0.31 mg/kg), N-nitrosodi-n-butylamine (0.083 mg/kg), N-nitroso-N-methylurea (0.56 mg/kg), N-nitroso-N-ethylurea (0.37 mg/kg), N-nitroso-N-butylurea (0.16 mg/kg), streptozotocin (20 mg/kg), N-nitrosomorpholine (0.4 mg/kg), N-nitrosopiperidine (2.22 mg/kg), N-nitrosopyrrolidine (5.0 mg/kg), 1-nitroso-2-imidazolidinone (0.31 mg/kg), and N-methyl-N'-nitro-N-nitrosoguanidine (5.57 mg/kg). The contemporary measurement of liver DNA fragmentation by the alkaline elution technique revealed that in our experimental conditions higher doses are needed to produce a statistically significant increase of DNA elution rate. This suggests that the viscometric method is capable of detecting smaller levels of N-nitroso compound-induced DNA fragmentation, but it does not exclude that the sensitivity of alkaline elution can be improved by appropriate modifications of the experimental procedure. With both techniques DNA damage was undetectable in liver of rats treated with 540 mg/kg of the non-hepatocarcinogen N-nitrosodiphenylamine. With the exception of N-nitrosodiethanolamine, that exhibited a plateau effect, all the other N-nitroso compounds examined displayed a linear dose-response curve over the entire wide range of doses tested. Consequently, a nonlinearity of the relationship between dose and tumor response cannot be attributed to a nonlinearity of the pharmacokinetic processes involved in the formation of DNA damage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3485-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Dose-response curves for liver DNA fragmentation induced in rats by sixteen N-nitroso compounds as measured by viscometric and alkaline elution analyses.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't