New test speeds detection of E. coli.

The biochemical effects of CHIP have been studied in C3H mice with and without transplanted mammary tumour. The maximum tolerated dose of CHIP was first determined by lethality and intestinal crypt assays to be 40mgkg-' and this dose was used to assay the time course of gastric distension and the pattern of drug distribution. A high level of CHIP uptake was found in liver as well as kidney. For this reason, tests for both kidney and liver damage were undertaken up to 60 days post-treatment using a dose of 10mgkg-1 Neoplatin for comparison. Despite the high level of platinum drug uptake in liver, there was no biochemical evidence of hepatocellular or cholestatic damage. From the renal point of view, there was the expected rise in serum urea after Neoplatin but not after CHIP and there was also a rise in urinary NAG after Neoplatin in tumour bearing mice. There was, however, evidence of suppression of protein levels including enzymes, following treatment with both drugs. Tumour-bearing mice respond differently from normal mice following treatment with platinum drugs. The study confirms that CHIP is less toxic than Neoplatin. The aim of this paper is to show that precise data can be obtained on the biochemical effects of cancer chemotherapy in experimental animals, and that this should include tumour-bearing animals. This is of particular importance since mouse and other small rodent data are often put forward as the main basis for a Phase I clinical trial. Neoplatin (cis dichlorodiammine platinum II) is a first generation platinum anticancer drug, and the activity and biochemical effects in humans have been well documented from clinical trials (Dentino et al., 1976; Wiltshaw, 1978). CHIP (cis dichloro trans-dihydroxy bis isopropylamine platinum IV), is a more soluble platinum complex, selected as a second generation drug (Shepherd et al., 1980) in the hope that it will be at least as effective an antitumour agent as Neoplatin, will have reduced toxic side effects (especially nephrotoxicity and nausea) and will not exhibit cross resistance with Neoplatin resistant tumours. CHIP is now in clinical trial (Creaven et al., 1983). In the experiments reported here, the maximum tolerated dose of Chip was first estimated from LDSO experiments and the gastrointestinal toxicity confirmed using assays of intestinal crypt damage and gastric distension. The distribution of CHIP in the mouse tissues was shown by radioactive platinum labelled CHIP incorporation and this confirmed the high levels of …