Dose addition and the isobole method as approaches for predicting the cumulative effect of non-interacting chemicals: a critical evaluation
Bosgra, S; van Eijkeren, JC; Slob, W
HERO ID
4733126
Reference Type
Journal Article
Year
2009
Language
English
PMID
| HERO ID | 4733126 |
|---|---|
| In Press | No |
| Year | 2009 |
| Title | Dose addition and the isobole method as approaches for predicting the cumulative effect of non-interacting chemicals: a critical evaluation |
| Authors | Bosgra, S; van Eijkeren, JC; Slob, W |
| Journal | Critical Reviews in Toxicology |
| Volume | 39 |
| Page Numbers | 418-426 |
| Abstract | Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael acceptors, and cellular damage can occur through alkylation of crucial cellular proteins and/or DNA. Alternatively, quinones are highly redox active molecules which can redox cycle with their semiquinone radicals, leading to formation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can cause severe oxidative stress within cells through the formation of oxidized cellular macromolecules, including lipids, proteins, and DNA. Formation of oxidatively damaged bases such as 8-oxodeoxyguanosine has been associated with aging and carcinogenesis. Furthermore, ROS can activate a number of signaling pathways, including protein kinase C and RAS. This review explores the varied cytotoxic effects of quinones using specific examples, including quinones produced from benzene, polycyclic aromatic hydrocarbons, estrogens, and catecholamines. The evidence strongly suggests that the numerous mechanisms of quinone toxicity (i.e., alkylation vs oxidative stress) can be correlated with the known pathology of the parent compound(s). |
| Doi | 10.1080/10408440902787592 |
| Pmid | 19514914 |
| Wosid | WOS:000273385500002 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | |WOS:000086082800001 |
| Is Public | Yes |
| Language Text | English |