Effect, carcinogenic screen

Named after its inventor, Bruce Ames, the test has become one of the common screening tests for measuring the potential carcinogenic effects of... 

Category A lists three types of studies for human health effects basic acute toxicity tests, a 28-day animal study (referred to in other discussions as a "sub-chronic" test), and a series of two (or more) screening tests for mutagenicity and carcinogenicity. 

Some of these problems can be overcome by the use of cell-based systems, in particular, primary hepatocytes. Hepatocytes closely simulate the metabolic systems found in the intact fiver and do not require additional cofactors for optimal enzyme activity. However, apart from greater technical difficulties in obtaining hepatocytes as opposed to S9 fraction, hepatocytes can effectively detoxify particular carcinogens and prevent their detection as mutagens. Despite these difficulties, hepatocytes have a role to play in mutagenicity screening, in both bacterial and mammalian-based systems (Tweats and Gatehouse, 1988). 

Looked at another way, the four major carcinogenic mechanisms are DNA damage, cell toxicity, cell proliferation and oncogene activation. Any effective program to identify those drags which have the potential to cause or increase the incidence of neoplasia in humans must effectively screen for these mechanisms (Kitchin, 1999). 

Jin T, Lin H, Xin P, et al. 1982. [Preliminary screening of mutagenic and carcinogenic effect of pesticides by inhibition test of DNA synthesis.] Zhonghua Yufangyixue Zazhi 16(3) 174-176. (Chinese)... 

Tretinoin or retinoic acid is the acid form of vitamin A. Actually it is the all-trans isomer of retinoic acid. It is an effective topical agent for acne vulgaris. Its mechanism of action is believed to be associated with increased epidermal cell turnover. Some 10% of the topically applied dose is absorbed, metabolized by the liver and excreted in the urine and bile. To be effective tretinoin should be applied in a concentration that results in mild irritation and erythema. Patients should be advised to avoid or minimize sun exposure and use a protective sun screen as animal studies have raised some concern about possible carcinogenic effects under the influence of ultraviolet radiation. There are no indications that topical tretinoin is associated with an increased risk for birth defects. 

---