Carcinogenicity study of fecapentaene-12 diacetate on skin painting in SENCAR mice

To investigate the effects of both diol esterification and coadministration with antioxidant on the tumorigenicity of fecapentaene-12 (FP-12) preparations, diacetylfecapentaene-12 (DAFP-12) in dimethylsulfoxide (DMSO) was applied to SENCAR mouse skin with or without the stabilizer, vitamin E, twice/week for 5 weeks, following which all animals were promoted for up to 25 weeks by weekly applications of 12-O-tetradecanoylphorbol-13-acetate (TPA). While positive controls receiving 7,12-dimethylbenz[a]anthracene (DMBA) instead of DAFP-12 in a similar protocol all developed papillomas (average of 23/animal), papilloma incidence in mice given DAFP-12 did not differ significantly from that of the vehicle control. We conclude that DAFP-12 shows little or no tumor initiating activity for mouse skin even when coadministered with vitamin E.     

Carcinogenicity of hydroxylated alkylnitrosoureas and of nitrosooxazolidones by mouse skin painting and by gavage in rats

The carcinogenic effectiveness of a number of nitrosoalkylamides related to nitrosoethylurea and nitroso-n-propylurea has been compared by topical application to Swiss mice and by intragastric administration to F344 rats. Nitrosohydroxyethylurea and the related cyclic nitrosamide, nitrosooxazolidone, were as potent as nitrosoethylurea as skin carcinogens, although the latter was a much weaker mutagen to Salmonella. When administered p.o., nitrosooxazolidone induced mainly forestomach tumors in rats, while nitrosohydroxyethylurea was very broadly acting, inducing neoplasms of the lung, forestomach, glandular stomach, colon, duodenum, and bone (osteogenic sarcomas). Nitroso-2-hydroxypropylurea, nitroso-3-hydroxypropylurea, and nitroso-5-methyloxazolidone were all much more potent carcinogens on mouse skin than was nitroso-n-propylurea, nitroso-5-methyloxazolidone being somewhat less effective than the nitrosoureas; the mutagenicity to Salmonella seemed not to be quantitatively related to carcinogenicity. Nitroso-5-methyloxazolidone given p.o. to rats induced mainly forestomach neoplasms and a few neoplasms of the duodenum, whereas similar treatment of rats with nitroso-2-hydroxypropylurea induced a high incidence of neoplasms of the thymus, some of the forestomach, and few at any other site.     

Carcinogenicity of chloroform

Carcinogenicity of chloroform for various dosage and route of administration was assessed in CBA X C57B1/6 mice in a chronic experiment (250 or 15 mg/kg body weight in vegetable oil, intra-esophageally via a probe; or 300; 30; 3; 0.3 or 0.03 mg/l in drinking water). Chloroform did not reveal its carcinogenic properties unless a dose of 250 mg/kg was given.     

和金属内植物有关的肿瘤发生

金属内植物用于治疗临床骨科疾病已有百年的历史。随着患者随访时间的延长，与金属内植物有关的疾病发生的数量和种类也在逐年增加。在植入手术以后，体液中金属离子的代谢对人体的影响以及金属内植物可能诱导内植物旁或远隔部位的肿瘤发生引起了人们的关注。文章总结近几十年来国内外对该领域的研究情况，旨在能对临床骨科医师就金属内植物的使用提高认识。     

Carcinogenicity of anticancer agents

Chemotherapeutic treatment for cancer has been successful in prolonging survival but it has also been demonstrated that survivors of cancer patients who had received chemotherapy with alkylating agents have an increased risk of second malignancies, mostly acute non-lymphatic leukemia. The purpose of this paper is to show practical problems pertaining to the development and clinical use of anticancer agents in terms of prevention of second cancers.     

Carcinogenicity of cytostatic triazenes

Introduction of the anticancer drug dacarbazine is the result of an attempt to design antagonists of purine biosynthesis. The mechanism of action of dacarbazine depends mainly on enzymatic transformation into as yet unknown reactive (electrophilic) intermediates. Recent studies have led to the identification and synthesis of 5-(3-hydroxymethyl-3-methyl)imidazole-4-carboxamide (HMTIC), a carbinolamine metabolite with methylating capacity. Although dacarbazine and related cytostatic triazenes are effective in the treatment of malignant melanoma and other human malignancies, dacarbazine has been demonstrated to be a carcinogen in laboratory rodents. Chronic administration of dacarbazine to rats of each sex induced predominantly thymic lymphosarcomas and mammary adenocarcinomas that were transplantable. Intraperitoneally injected 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC), a metabolite of dacarbazine, induced a high incidence of mammary adenofibromas and a low incidence of uterine leiomyosarcomas. Animals treated with 5-diazoimidazole-4-carboxamide developed a low incidence of thymic, stomach, bladder or mammary tumours. Animals receiving 5-aminoimidazole-4-carboxamide developed a variety of tumours. No secondary malignancy has been reported in humans after treatment with dacarbazine alone. Despite their adverse effects, dacarbazine and related cytostatic triazene derivatives are useful clinically since their haematological toxicity is relatively moderate. As a rule, they are not cross-resistant with nitrogen mustard alkylating agents. It is hoped that research and development of second-generation N-(1-hydroxyalkyl)triazene compounds will lead to improvements in their clinical efficacy.