The potential of cis-diamminedichloroplatinum(II) (CDDP), trans-di(2-nitroimidazole)dichloro-platinum(II) (NIPt), trans-di(2-amino-5-nitrothiazole)dichloroplatinum(II) (Plant), cis-(1,2-diamino-4-nitrobenzene)dichloroplatinum(II) (Plato), and cis-di-pyridinedichloroplatinum(II) (PyPt) to act as chemosensitizers of mitomycin C cytotoxicity toward EMT6 cells under oxygenated and hypoxic conditions has been assessed. Cells were given a 1 h treatment with the platinum complex under oxygenated or hypoxic conditions and then an additional one hour of exposure to the combination. Two concentrations of each platinum complex, 0.1 and 0.01 microM, were tested in combination with mitomycin C at 1, 0.1 and 0.01 microM. The results were analyzed via isobolograms. Under oxygenated conditions the combinations of the various platinum complexes and mitomycin C produced approximately a 2-3-fold enhancement in cell killing. Under hypoxic conditions enhancements of 5-fold, 20-fold and 60-fold were obtained with CDDP and 1, 0.1 and 0.01 microM mitomycin C, respectively. The combinations of 0.1 microM NIPT and mitomycin C under hypoxic conditions were 30-60-fold more cytotoxic than expected by additivity. With 0.01 microM NIPT a 15-23-fold enhancement of mitomycin C cytotoxicity was observed. The Plant-mitomycin C combinations produced a 5-14-fold enhancement in cell killing under hypoxic conditions. Under hypoxic conditions the combinations of 0.1 microM Plato and mitomycin C were 30-60-fold more cytotoxic than expected. At 0.01 microM Plato an 8-16-fold enhancement in cytotoxicity was observed under hypoxic conditions. PyPt and mitomycin C produced an 8-16-fold enhancement in cytotoxicity under hypoxic conditions. Overall, the platinum complexes containing radiosensitizing nitroaromatic groups were no more active in producing enhanced effects than cis-diamminedichloroplatinum(II).

Urinary psi excretion is independent of the main indices of tumour activity in myelomatosis (serum paraprotein, serum beta 2-microglobulin, serum creatinine and urinary light chain production). The mean (+/- s.d.) psi at presentation was 40.7 +/- 22.6 nmol. mumol ucr-1, compared to 25.4 +/- 4.8 nmol. mumol ucr-1 in controls. Urinary psi levels at presentation are significantly related to prognosis, the higher the level the poorer the prognosis. However, when these levels have been stratified according to the corresponding level of serum beta 2m, the level adds little as a prognostic factor.

Attention has recently focused on the possible teratogenic effects of the combination antiemetic doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride (Debendox/Bendectin) prescribed to pregnant women. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC), a case-control investigation has analysed data derived from interview reports and medical records of 555 mothers of children (under 15 years) with cancer and 1110 mothers of matched control children. Separate analyses of interview reports and medical records both suggested that antiemetic ingestion during the index pregnancy does not increase the risk of developing childhood malignant disease in the exposed foetus. No dose-response relationship was evident. The lack of any significant relative risks held good for diagnostic sub-groups and when the trimester of ingestion was considered. Our results suggest that antimetics of this type are unlikely to be transplacental carcinogens.

The present investigation shows the effect of vitamin A deficiency on the initiation and postinitiation phases of benzo(a)pyrene-induced lung carcinogenesis in male Wistar rats. Lung tumours were induced by giving three intratracheal instillations, one week apart, of 10 mg benzo(a)pyrene per instillation. Maximum tumour incidence (100%) and tumour burden per rat was found in rats which were kept on vitamin A deficient diet for 4 weeks prior to the first administration and 8 weeks after the last administration of benzo(a)pyrene. Rats in which vitamin A deficiency was terminated after the last administration of the carcinogen had 83% tumour incidence, whereas corresponding control pairfed animals had 39% incidence of tumours. These data represent the values obtained 32 weeks after the last administered dose of the carcinogen and indicate the role of vitamin A, both in the initiation as well as in the postinitiation phases of lung carcinogenesis. Images Figure 1 Figure 2

A study of 361 female melanoma patients and age matched controls was conducted in the four western provinces of Canada. Analysis of reproductive factors showed a significant negative association between number of livebirths and risk of melanoma. The relationship persisted for superficial spreading melanomas after adjustment for host pigmentation factors, freckling, and educational status. An inverse association between bilateral oophorectomy and risk of superficial spreading melanoma was also seen. No association was found between risk of melanoma and age at first birth, age at menarche and age at natural menopause. No association was found between risk of superficial spreading or nodular melanoma and use of either oral contraceptives or menopausal oestrogens.

Growth delay by melphalan of two fibrosarcomas in CBA mice was prolonged by intraperitoneal (i.p.) verapamil, 10 mg kg-1. Verapamil also increased the area under the blood concentration time curve and the gastrointestinal toxicity of melphalan. Verapamil promoted melphalan cytotoxicity to murine bone marrow both in vivo, by CFU-S assay, and in vitro, by CFU-GM assay. In 1 microgram ml-1 [14C]-melphalan, verapamil (10 micrograms ml-1) increased by 1.5 times the [14C]-melphalan accumulation by murine bone marrow, reversibly and independently of external calcium. Efflux of [14C]-melphalan from murine bone marrow was retarded by verapamil. Verapamil increased [14C]-melphalan uptake by disaggregated fibrosarcoma cells but had no effect on melphalan accumulation and cytotoxicity in human bone marrow. Although verapamil affected melphalan pharmacokinetics, enhancement of cellular melphalan uptake by verapamil in murine fibrosarcoma and bone marrow appeared to account for much of the increase in melphalan cytotoxicity. The lack of potentiation of melphalan by verapamil in human marrow suggests differences in melphalan transport or in verapamil membrane interactions in mouse and man.

The prevalence (lifetime occurrence) rate of cancers of the reproductive system (uterus, ovary, cervix and vagina) and breast cancer was determined for 5,398 living alumnae, 2,622 of whom were former college athletes and 2,776 non-athletes, from data on medical and reproductive history, athletic training and diet. The former athletes had a significantly lower risk of cancer of the breast and reproductive system than did the non-athletes. The relative risk (RR), non-athletes/athletes, for cancers of the reproductive system was 2.53. 95% confidence limits (CL) (1.17, 5.47). The RR for breast cancer was 1.86, 95% CL (1.00, 3.47). The analysis controlled for potential confounding factors including age, family history of cancer, age of menarche, number of pregnancies, use of oral contraceptives, use of oestrogen in the menopausal period, smoking, and leanness. Of the college athletes, 82.4% had been on pre-college teams compared to 24.9% of the college non-athletes. We conclude that long term athletic training may lower the risk of breast cancer and cancers of the reproductive system.

Evidence of epidemicity of nasopharyngeal carcinoma (NPC) was sought in Greenland Inuits, who have a high incidence of this cancer, by examining the births of NPC cases for evidence of clustering in time and space. Births of cases were concentrated in autumn and winter. Fifty-four cases were analysed, and a two-fold excess of clustering within one year was observed, both within single districts and between adjacent districts. This excess was not significant at the 5% level; about 90 cases would have been required to confirm the observed effect at this level of significance. It is suggested that a search for space-time clustering of NPC cases in larger high-risk populations might prove more fruitful.