Carcinogenic activity structure relationship

Immediately after the first few carcinogenic hydrocarbons were identified, scientists puzzled over the developing structure-activity relationships and tried to identify the structural features of the hydrocarbons which are associated with their carcinogenic activity. 

It is not possible on the basis of present knowledge of the relationship of chemical structure to the carcinogenic activity of a chemical to predict how many of the millions of compounds in nature, or the tens of thousands of compounds in commerce, are carcinogenic. Although relatively few chemicals have been observed to cause cancer in human populations, those that have (Thble 5.1), and the himdreds of other substances for which there is some evidence of carcinogenicity in laboratory animals (Thble 5.2), include compounds of widely diverse structures. 

Blake BW, Enslein K, Gombar VK, et al. 1990. Salmonella mutagenicity and rodent carcinogenicity quantitative structure-activity relationships. Mutat Res 241(3) 261-271. 

Q. Dai and C. Shi, Kexue Tangbao, 30, 52 (1985). Structure-Carcinogenic Activity Relationship of Alkly-Substituted Polycyclic Aromatic Hydrocarbons by Pattern Recognition by Computer. 

The relationship between carcinogenic activity and chemical properties is far from clear, but the possibility of uncovering this relationship has inspired a tremendous amount of research in the fields of synthesis and of structure and reactivity. 

Arcos, J.C. (1987). Structure-Activity Relationships Criteria for Predicting Carcinogenic Activity of Chemical Compounds. Environ.Sci.Technol,21,743-745. 

Vendrame, R., Braga, R.S., Takahata, Y. and Galvao, D.S. (1999). Structure-Activity Relationship Studies of Carcinogenic Activity of Polycyclic Aromatic Hydrocarbons Using Molecular Descriptors with Principal Component Analysis and Neural Network Methods. J.Chem.lnf. Comput.Sci.,39,1094-1104. 

Benigni R. Chemical structure of mutagens and carcinogens and the relationship with biological activity. J Exp Clin Cane Res 2004 23 5-8. 

Arcos, J.C. (1987) Structure-activity relationships criteria for predicting carcinogenic activity of chemical compounds. Environ. Sci. Technol., 21, 743-745. 

Structure-activity relationship (SAR) analysis is essential for the development of pesticides and for the evaluation of cancer hazard and risk assessment. The critical factors that should be considered in SAR analysis and the profile of typical potent carcinogens are discussed. A scheme combining structural and functional criteria for suspecting chemical compounds of carcinogenic activity is presented. Selected classes of pesticides with carcinogenic potential are reviewed to exemplify structural and/or functional features responsible for their carcinogenic activity. 

The biogenetic structural relationships and structure-activity relationships of the diterpenoid skin irritants and co-carcinogens of the Euphorbiaceae and Thymelaceae have been described in a number of reviews.Baliospermum montanum (Euphorbiaceae) contains the orthoester montanin (111) and baliospermin (112) together with some 12-deoxyphorbol-13-esters. A number of new highly irritant 1-alkyl-daphnane orthoester derivatives [(113) and the corresponding 3-ketone] have been obtained from the Thymelaceae. The Chinese... 

Structure-Carcinogenic Activity Relationship Studies of Polycyclic Aromatic Hydrocarbons (PAHs) with Pattern-Recognition Methods. 

Enslein, K. An overview of structure-activity relationships as an alternative to testing in animals for carcinogenicity, mutagenicity, dermal and eye irritation, and acute oral toxicity. Toxicol Industrial Health 1988 4 479-98. 

Benigni R, Giuliani A. Quantitative structure-activity relationship (QSAR) studies of mutagens and carcinogens. Med Res Rev 1996 16 267-84. 

Woo Y-T, Lai DY, Argus ME, Arcos JC. Development of structure-activity relationship rules for predicting carcinogenic potential of chemicals. Toxicol Lett 1995 79 219-28. 

The Danish EPA has developed an advisory list for self-classification of dangerous substances including 20 624 substances. The substances have been identified by means of QSAR models (Quantitative Structure-Activity Relationship) as having acute oral toxicity, sensitization, mutagenicity, carcinogenicity, and/or danger to the aquatic environment. 

Helma C (2006) Lazy structure-activity relationships (lazar) for the prediction of rodent carcinogenicity and salmonella mutagenicity. Mol Divers 10 147-158... 

Although traditional octanol/water distribution coefficients are still widely used in quantitative structure-activity relationships (QSAR) and in ADME/ pharmacokinetic (PK) studies, alternatives have been proposed. To cover the variability in biophysical characteristics of different membrane types, a set of four solvents has been suggested - sometimes called the critical quartet [49-51], The 1,2-dichloroethane (DCE)/water system has been promoted as a good alternative to alkane/water due to its far better dissolution properties [50, 51], but it may be used only rarely due to its carcinogenic properties. 

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