N-Nitrosomethylurea (NMU) (20 mg/kg) was i.p. administered to rats on the 21st day of pregnancy. A decrease of glucose utilisation in the oral glucose tolerance test was found in 3 month old female progeny of NMU-treated rats. The serum insulin level did not differ from control, but serum cholesterol level was higher in offspring of NMU-treated rats. The ability of diethylstilboestrol to inhibit compensatory ovarian hypertrophy was decreased in female hemicastrated 3 month old rats whose mothers were treated with NMU. Postnatal administration of the antidiabetic drug buformin decreased the malignant neurogenic tumor incidence 3.5 times (to rats transplacentally treated with NMU).

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel-5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno-stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.

Dioxadet and cisplatin show similar efficacy in the CIPC route. Compared with CIPC IP chemotherapy by chemoperfusions is more effective for both the drugs. Dioxadet in HIPEC showed highest survival benefit whereas largest effect during NIPEC is achieved with cisplatin.

Formation and loss of methylated purines in DNA of various fetal and maternal tissues were measured up to 7 days following intravenous administration of N-[14C]methyl-N-nitrosourea to rats on the 21st day of gestation. Methylation products were detected in all tissues examined, the level in maternal liver being higher than in other tissues. The concentrations of 7-methylguanine and 3-methyladenine decreased faster in fetal than in corresponding maternal tissues, due to a higher rate of DNA synthesis in fetal tissues, as determined by incorporation of labelled thymidine. Removal of the promutagenic DNA lesion O6-methylguanine was most efficient in maternal and fetal liver; but it was very poorly repaired in kidney and brain. The persistence of O6-methylguanine relative to 7-methylguanine was highest in the DNA of fetal brain. The principal targets for the transplacental carcinogenic effect of N-methyl-N-nitrosourea under these experimental conditions were fetal neurogenic tissue and kidney; and malignant tumors developed at these sites in 31-34% and 15-16% of male and female descendants, respectively. These results support the concept that a complex interaction between DNA alkylation, repair and replication is the molecular basis of initiation of carcinogenesis by alkylating agents.