23 research outputs found
In silico toxicology protocols
The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information
Specificity of deoxycytidylate antibodies
Antibodies to deoxycytidylate (dpC) were elicited in rabbits using a thyroglobulin (Tg) conjugate of dpC. The specificity of the antibodies was determined by measuring the inhibition of the binding of [3H]dpC to the antibodies by various non-radioactive nucleotides or derivatives. The antibodies were found to distinguish dpC from pC and DNA from RNA, probably due to their specificity for the conformation of the deoxycytidylate
Deoxycytidylate antibodies:elicitation, purification and studies on interaction with ligands
To elicit antibodies specific to deoxycytidylate (dpC), rabbits were immunized with dpC conjugates of the carrier proteins bovine serum albumin (BSA) and thyroglobulin (Tg). Antibodies thus formed, when analyzed by Ouchterlony-double diffusion and their binding to [3H]dpC using nitrocellulose filter assay and equilibrium dialysis, showed that the BSA conjugate of dpC is not effective, whereas the Tg conjugate of dpC (Tg-dpC) is effective in eliciting dpC specific antibodies. The antisera raised against Tg-dpC was purified on AH-sepharose-dpC and cellulose-oligo-dpC affinity columns using dpC for elution. Tg-dpC antisera could be separated into 3 fractions, namely, antibodies to Tg, antibodies specific to dpC, and antibodies to the linkage region of the carrier protein and hapten. The affinity constant for the binding of anti-dpC Fab fragments to dpC by equilibrium dialysis was at and at . \triangle and \triangle for the binding were -10 kcal/mol and -9 cal/deg/mol, respectively
Specificity of deoxycytidylate antibodies
Antibodies to deoxycytidylate (dpC) were elicited in rabbits using a thyroglobulin (Tg) conjugate of dpC. The specificity of the antibodies was determined by measuring the inhibition of the binding of [3H]dpC to the antibodies by various non-radioactive nucleotides or derivatives. The antibodies were found to distinguish dpC from pC and DNA from RNA, probably due to their specificity for the conformation of the deoxycytidylate
Comparison of Biological and Chemical Predictors of Dermal Carcinogenicity of Petroleum Oils
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Creating context for the use of DNA adduct data in cancer risk assessment: I. Data organization
The assessment of human cancer risk from chemical exposure requires the integration of diverse types of data. Such data involve effects at the cell and tissue levels. This report focuses on the specific utility of one type of data, namely DNA adducts. Emphasis is placed on the appreciation that such DNA adduct data cannot be used in isolation in the risk assessment process but must be used in an integrated fashion with other information. As emerging technologies provide even more sensitive quantitative measurements of DNA adducts, integration that establishes links between DNA adducts and accepted outcome measures becomes critical for risk assessment. The present report proposes an organizational approach for the assessment of DNA adduct data (e.g., type of adduct, frequency, persistence, type of repair process) in concert with other relevant data, such as dosimetry, toxicity, mutagenicity, genotoxicity, and tumor incidence, to inform characterization of the mode of action. DNA adducts are considered biomarkers of exposure, whereas gene mutations and chromosomal alterations are often biomarkers of early biological effects and also can be bioindicators of the carcinogenic process