ABSTRACT
I. INTRODUCTION In vitro mutagenesis tests are genetic toxicological studies, at the early drug development, to provide initial assessment of the safety profile of potential and promising pharmaceutical entities. Short-term assays using mammalian Chinese hamster ovary (CHO) cells for identification of mutagens and potential carcinogens include the hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) mutagenesis assay, sister chromatid exchange (SCE), and chromosome aberration cytogenetic assays. The response variables of these in vitro assays are counts. The count data from the CHO/HGPRT test, as shown in Snee and Irr (1981), do not follow a Poisson distribution whereas, as demonstrated by Mar golin et al. (1986), the Poisson distribution fits the SCE counts quite satisfactorily. The design and statistical methods for analysis of the counts data from CHO/HGPRT assays and SCE tests based on CHO cells will be introduced and discussed. Section II provides the back ground and a brief description of the experimental procedure for a
CHO/HGPRT assay. Statistical designs and rationale for the transfor mation recommended by Snee and Irr (1981) will be given in Section III. The background and a short introduction to the in vitro cytogenetic sister chromatid exchange and chromosome aberration using Chinese hamster ovary cells will be provided in Section IV. Section V presents the statistical design and rationale of the recommended statistical methods for analysis of SCE counts by Margolin et al. (1986). Final remarks and discussion will be given in Section V.
