Summary The induction of chromosome damage by the Platinum complex CHIP in Chinese hamster ovary (CHO) cells has been studied, together with the relationship between cell survival and aberration frequency. The type and frequency of chromosome aberrations observed in asynchronous and G, phase treated cells indicated a similar mode of action to that of bifunctional alkylating agents. A log-linear relationship was observed between the frequency of chromatid aberrations (excluding gaps) and the level of survival after CHIP treatment, with approximately one aberration per cell corresponding to 37% survival.Cis dichloro-bis (isopropylamine) trans dihydroxy platinum IV-CHIP-is one of the new platinum co-ordination complexes in the group of potential antitumour agents, whose cytotoxic action has now been studied extensively. It can be compared with another platinum complex cis-dichloro-bis (cyclopentylamine) platinum (II), PAD, which although insoluble in water was found to have a high antitumour activity and a large therapeutic index (235), (Connors et al., 1972). In contrast, CHIP is highly water soluble and this has encouraged further investigation into its mode of action.Results from several workers indicate that DNA is the primary intracellular target for the cytotoxic action of the platinum complexes, where inter-and intra-strand crosslinks are produced (Roberts & Pascoe, 1972;Kelman et al., 1977). These effects of platinum complexes on DNA point to a similar mode of action to that observed with bifunctional alkylating agents; i.e. the production of "delayed type" chromosome aberrations as a result of DNA synthesis on a damaged template (Bender et al., 1974).Studies were undertaken to examine this possibility and to understand better the mechanism underlying the cytotoxic action of CHIP. In this paper the results of the investigation of the production of chromosome aberrations by CHIP in

Summary A study of C3H mice implanted with mammary tumours has shown that the levels of serum total protein, alanine transaminase and alkaline phosphatase are all lower than those found in normal mice, while aspartate transaminase is higher. Serum urea values were similar to normal levels, but creatinine was lower in males and higher in females. In the male mice, urine protein and urine N-acetyl-,B-D-glucosaminidase (NAG) activity were lower than in normal mice.Comparisons were made with age and sex matched controls which was found to be important for alkaline phosphatase, as this was shown to decrease with increasing age of the mice over the period from 10-30 weeks of age.The analyte values found in this study provide useful base-line data for assessing biochemical toxicity of cancer chemotherapy agents. It has been shown that some of these values can vary with age, or can be different if tumour-bearing mice are used instead of normal mice.

Summary.-A new, stable platinum coordination complex (FLAP) containing the 5-nitroimidazole, metronidazole, has been prepared and characterized. The squareplanar platinum(II) complex has two metronidazole molecules and two chlorine atoms in the cis configuration. The properties of FLAP differ significantly from metronidazole alone or other platinum complexes tested in the same system. It has a low toxicity towards Chinese hamster ovary cells and is a very effective radiosensitizer toward hypoxic cells in vitro: a one-h pretreatment with a non-toxic dose of 50 ytM gave an enhancement ratio of 2-4. No potentiation of aerated cells to Xirradiation damage was observed after a similar schedule of pretreatment at the higher dose of 100 /uM FLAP.

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CHIP (cis-dichlorobis isopropylamine trans-dihydroxy platinum IV) is a second-generation platinum co-ordination complex which potentiates the effects of radiation. Comparisons of the biological effects of CHIP and X rays upon Chinese hamster (ovary) cells have shown similarities with respect to the shape of the dose-response curves, clone size distributions and perturbation of the cell cycle. Unlike irradiated cells however, CHIP-treated cells showed no recovery from sublethal damage and no variation in sensitivity throughout the cell cycle. CHIP is a radiomimetic drug in some respects but not in others.