Carcinogenicity of bleomycin sulfate and peplomycin sulfate after repeated subcutaneous application to rats. 1984

M Habs, and D Schmähl

Bleomycins (BLM) are widely used as antineoplastic agents either alone or in combination regimens. Results of earlier studies in experimental animals were said to be inadequate to evaluate the carcinogenicity of BLM, which is a known mutagen. In a dose-response study, BLM and peplomycin (PEP) were investigated in Sprague-Dawley rats of both sexes. For the first 10 weeks weekly doses of 0.35, 0.70, 1.40, and 2.80 mg/kg BLM and of 0.32, 0.63, 1.25, 2.50, and 5.0 mg/kg PEP were applied subcutaneously (BLM: 30 male and 30 female rats/group; PEP: 25 male and 25 female rats/group). In the case of BLM, thereafter the doses were given once every fortnight either for 1 year (BLM: 1.40 and 2.80) or for life (lower doses). In the case of PEP, application of the high doses was stopped after the 13th time (5.0: 10 X 1/week and 3 X 1 every 2 weeks) and the 19th application (2.5 mg: 10 X 1/week and 9 X 1/every 2 weeks). After the 10th dosing, the remaining groups were treated once every fortnight for life. 60 male and 60 female rats served as solvent-treated (physiological saline) controls. The animals were observed for life. Repeated doses of BLM and PEP reduced body weight and life expectancy of the animals in a dose-related pattern. Tubular cell damages and cell proliferations were seen as a symptom of major toxicity in the kidneys. In this model BLM and PEP are carcinogenic: treatments resulted in significant dose-related incidences of animals with tumors at the site of application (fibrosarcomas) and with renal tumors (adenomas, adenocarcinomas, sarcomas).

UI MeSH Term Description Entries
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D007680 Kidney Neoplasms Tumors or cancers of the KIDNEY. Cancer of Kidney,Kidney Cancer,Renal Cancer,Cancer of the Kidney,Neoplasms, Kidney,Renal Neoplasms,Cancer, Kidney,Cancer, Renal,Cancers, Kidney,Cancers, Renal,Kidney Cancers,Kidney Neoplasm,Neoplasm, Kidney,Neoplasm, Renal,Neoplasms, Renal,Renal Cancers,Renal Neoplasm
D008297 Male Males
D001761 Bleomycin A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. BLEO-cell,Blanoxan,Blenoxane,Bleolem,Bleomicina,Bleomycin A(2),Bleomycin A2,Bleomycin B(2),Bleomycin B2,Bleomycin Sulfate,Bleomycins,Bleomycinum Mack,Bléomycine Bellon,BLEO cell,BLEOcell,Bellon, Bléomycine,Mack, Bleomycinum,Sulfate, Bleomycin
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000903 Antibiotics, Antineoplastic Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. Antineoplastic Antibiotics,Cytotoxic Antibiotics,Antibiotics, Cytotoxic

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