Statistical analysis of interactive cytotoxicity in human epidermal keratinocytes following exposure to a mixture of four metals

Characterization of gene expression changes associated with MNNG, arsenic, or metal mixture treatment in human keratinocytes: application of cDNA microarray technology.

“…Alterations in gene expression that differ depending on whether As is alone or mixed with other metals are also highly interesting and may potentially help us to understand the dose-dependent metal-metal interactions we have observed in these cells in other shortterm cytotoxicity studies in the lab (11,47). For example, in contrast to the situation in As-High, only one of the same DNA repair genes, HNTH1, was induced in cells treated with the As-containing metal mixture, despite the fact that the concentration of As was the same in both cultures.…”

Experimental designs for mixtures of chemicals along fixed ratio rays.

“…The interaction index, introduced by Berenbaum (12), provides a convenient method to determine and characterize departures from additivity for a combination of c > 2 or 3 components. The interaction index, II, is defined by [1] where c is the number of components, X 1 , X 2 ,…,X c are the doses in combination associated with a desired effect, and ED 100µ (CHEM i ), i = 1,…,c is the dose of the ith component that, when administered alone, produces the same effect. When the interaction index, defined in Equation 1, is equal to 1, the c components interact additively.…”

“…Details of the experimental protocol and methods are described elsewhere (1,24) and are not included here. The summary statistics for the LD 50 mixture data presented in Table 1 are linearized cytotoxicity response data from Gennings et al (1).…”

“…Of ultimate interest in such studies is the determination and characterization of interactions among the components in a mixture. For example, Gennings et al (1) report on a study of the nature of the interaction involving the mixture of four metals. The four metals chosen for the study were arsenic (As), cadmium (Cd), chromium (Cr), and lead (Pb), which are among the top contaminants in site frequency count by the Agency for Toxic Substances and Disease Registry (ATSDR) Completed Exposure Pathway Site Count Report (2).…”

“…Chemical Mixtures • Mixtures of chemicals along fixed ratio rays a Data from Gennings et al (1). b LD 50 mixing ratio (7.7 µM, 4.9 µM, 6.1 µM, and 100 µM) for As, Cr, Cd, and Pb, respectively.…”