Abstract:
:Chinese hamster cells (V79) were treated with ethylnitrosourea (ENU) and cis-diamminedichloroplatinum(II) (DDP) alone and in combination. Sister chromatid exchanges (SCEs) were quantified as measures of genotoxicity of the two agents. The combination experiment employed a factorial design in which cells were treated, in various concentration combinations, with both agents simultaneously. Response surface methodology, using a polynomial model based on a negative binomial distribution of SCE events, was employed for analysis of the interactions of the two genotoxic agents. The negative binomial distribution, a generalization of the Poisson distribution, is required since SCEs are discrete variables which, under the conditions of these experiments, have a distribution which exhibits extra-Poisson variability. The model of the ENU/DDP combinations indicated an increasingly less-than-additive effect resulting from increasing concentrations of each agent in the combination. The analysis of these experiments demonstrates the usefulness of a powerful statistical procedure for evaluating the biological effects resulting from exposure to multiple cytotoxic agents. The methodology can be used with many other types of endpoints and is not limited by the number of treatment agents.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Solana RP,Chinchilli VM,Wilson J,Carter WH Jr,Carchman RAdoi
10.1016/0041-008x(86)90117-1subject
Has Abstractpub_date
1986-09-15 00:00:00pages
231-8issue
2eissn
0041-008Xissn
1096-0333journal_volume
85pub_type
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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