chemical mutagens capable of inducing high frequencies of mutation at high 

 levels of survival (17). Concern also stemmed from the reaUzation that man was 

 greatly expanding the number of compounds theoretically capable of 

 increasing mutation frequencies beyond present 'spontaneous' levels. As 

 recently stated at an open meeting sponsored by the United States Department 

 of Health, Education and Welfare on the value of selected test systems to 

 detect and assess the mutagenic activity of chemicals (21), a human disease 

 burden exists which is of genetic origin. Increases in mutation frequency can be 

 expected to enlarge this burden, and many classes of chemicals already in the 

 environment are known to include genetic toxicants. Although uncertainty 

 remains regarding the precise impact such compounds might have upon human 

 health, there is justification for apprehension (15). 



Genetic toxicology, a new branch of toxicology concerned with the 

 identification and evaluation of DNA-damaging agents (carcinogens, mutagens 

 and some teratogens), may be broadly divided into (a) screening tests for 

 identification of potential toxicants, (b) procedures for estimating risk, and (c) 

 techniques for population monitoring. Screening involves primarily the use of 

 rapid, inexpensive assays which detect agents capable of damaging or altering 

 DNA. Because DNA is chemically and structurally similar in most organisms, 

 and is considered the probable target of genetic toxicants, any organism or 

 appropriate part thereof may be theoretically employed as a screening tool. 

 Accordingly, viruses (18), a variety of microbial systems (3,36), cultured 

 animal cells (14, 39, 26), Drosophila (2, 48), and various subcellular assays 

 designed to measure effects directly on DNA (47, 49) are widely used for 

 screening purposes. Several short-term tests utilizing intact mammals are also 

 available for screening (31). 



This paper is concerned with the application of an in vitro mammalian cell 

 assay utiHzing nutritional markers as an indicator system for genetic toxicants 

 detected as mutagens. Major objectives are to (a) outHne techniques for 

 measuring the acute toxicity of chemicals to cuhured cells, (b) qualitatively 

 describe the CHO Cell/BrdU-VL system as an assay for mutation, (c) present 

 data relative to the mutagenic potential of a series of compounds known to 

 accumulate in the tissues of edible marine organisms (41 , 45, 52) or which have 

 been associated with the occurance of neoplasias in such organisms (8, 51), and 

 (d) illustrate some additional end points, as well as some potential problems, 

 pertinent to the application of in vitro cell assays. A detailed description of 

 equipment, reagents, special techniques and experimental procedures relevant 

 to the CHO Cell/BrdU-VL system will not be given here. A general protocol for 

 this assay has been pubUshed by Kao and Puck (28). Our modifications to their 

 procedure will be described elsewhere (33). 



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