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PubMed1981

Iatrogenic carcinogenesis.

In a wider sense iatrogenic carcinogenesis means the induction of cancer by medical treatment. Some drugs have been now identified to be carcinogenic not only in experimental animals but also in man. For example, chlornaphazine used in the treatment of polycythemia has been proved to induce bladder cancer in 30% of the patients treated. This is also true for alkylating agents which are used as cytostatics in cancer treatment. Adjuvant chemotherapy must be used with due caution. There is probably one iatrogenic carcinoma in 10,000 cases. Hence, it is important to analyze the risk-benefit ratio of such drugs.

2-Naphthylamine↗
PubMed2003

Chlornaphazine and chlorambucil induce dominant lethal mutations in male mice.

Two antineoplastic agents, chlornaphazine (CN) and chlorambucil (CHL), were tested for the induction of dominant lethal mutations in male mice. Both compounds are nitrogen mustard derivatives and have been shown to be genotoxic in a variety of organisms. CN was administered intraperitoneally to DBA/2J male mice at a dosage of 0, 500, 1000, or 1500 mg/kg body weight (bw). Immediately following treatment, each male was mated at 4-day intervals to two virgin C57BL/6J females. CHL was administered intraperitoneally to C3H/HeJ and DBA/2J males at a dosage of 0, 2.5, or 5.0 mg/kg bw. These males were mated at weekly intervals to two virgin T-stock females. CN and CHL clearly induced dominant lethal mutations. CN induced dominant lethal effects in all post-meiotic germ-cell stages of treated DBA males, with a clear dose-response relationship. The results with CHL-treated DBA males indicated that all post-meiotic germ-cell stages, except late-spermatids, were affected by CHL treatment, while in C3H males, CHL induced dominant lethal effects in all post-meiotic germ-cell stages. A dose-response relationship was also observed with CHL in C3H male mice. In the present experiments, regardless of the agent or the mouse strain used, spermatids appeared to be the germ-cell stage most sensitive to dominant lethal induction.

Animals↗
PubMed1974

An analysis of survival in haploid and diploid cell cultures after exposure to ICR acridine half-mustard compounds mutagenic for bacteria.

Population changes induced by acridine mustards in haploid and diploid cultured cell lines from Rana pipiens were compared to test the expectation that recessive mutations will be expressed in diploid cells with a frequency equal to the square of that in haploid cells, and to investigate the usefulness of such comparison for the screening of possible mutagens. The differences in survival frequency after treatment were much smaller than predicted on the basis of the expression of lethal (recessive) mutations alone. Survival was also affected by culture conditions, drug-resistance phenomena, and other cell properties. It is suggested that with the evolution of epigenetic processes for the production of stable phenotypes, the vertebrate cell also acquired more efficient means to prevent the expression of gene mutation and that the acridine compounds may affect both epigenetic and genetic changes.

Acridines↗