Skip to main content
padlock icon - secure page this page is secure

Structure–activity relationship models for rat carcinogenesis and assessing the role mutagens play in model predictivity

Buy Article:

$61.00 + tax (Refund Policy)

We previously demonstrated that fragment based cat-SAR carcinogenesis models consisting solely of mutagenic or non-mutagenic carcinogens varied greatly in terms of their predictive accuracy. This led us to investigate how well the rat cancer cat-SAR model predicted mutagens and non-mutagens in their learning set. Four rat cancer cat-SAR models were developed: Complete Rat, Transgender Rat, Male Rat and Female Rat, with leave-one-out (LOO) validation concordance values of 69%, 74%, 67% and 73%, respectively. The mutagenic carcinogens produced concordance values in the range 69–76% compared with only 47–53% for non-mutagenic carcinogens. As a surrogate for mutagenicity, comparisons between single site and multiple site carcinogen SAR models were analysed. The LOO concordance values for models consisting of 1-site, 2-site and 4+-site carcinogens were 66%, 71% and 79%, respectively. As expected, the proportion of mutagens to non-mutagens also increased, rising from 54% for 1-site to 80% for 4+-site carcinogens. This study demonstrates that mutagenic chemicals, in both SAR learning sets and test sets, are influential in assessing model accuracy. This suggests that SAR models for carcinogens may require a two-step process in which mutagenicity is first determined before carcinogenicity can be accurately predicted.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
No Metrics

Keywords: cancer; multisite carcinogens; mutagenic carcinogens; non-mutagenic carcinogens; structure–activity relationship

Document Type: Research Article

Affiliations: 1: James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA 2: Gnarus Systems, Inc., Louisville, KY, 40202, USA

Publication date: June 3, 2014

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more