Investigations into the lymphopaenic and immunosuppressive properties of the antitumour agent, mitoclomine.
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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.
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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.
BACKGROUND: The stimulatory effect of CO2 on ethylene evolution in plants is known, but the extent to which ethylene controls photosynthesis is not clear. Studies on the effects of ethylene on CO2 metabolism have shown conflicting results. Increase or inhibition of photosynthesis by ethylene has been reported. To understand the physiological processes responsible for ethylene-mediated changes in photosynthesis, stomatal and mesophyll effects on photosynthesis and ethylene biosynthesis in response to ethephon treatment in mustard (Brassica juncea) cultivars differing in photosynthetic capacity were studied. RESULTS: The effects of ethephon on photosynthetic rate (PN), stomatal conductance (gS), carbonic anhydrase (CA) activity, 1-aminocyclopropane carboxylic acid synthase (ACS) activity and ethylene evolution were similar in both the cultivars. Increasing ethephon concentration up to 1.5 mM increased PN, gS and CA maximally, whereas 3.0 mM ethephon proved inhibitory. ACS activity and ethylene evolution increased with increasing concentrations of ethephon. The corresponding changes in gs and CA activity suggest that the changes in photosynthesis in response to ethephon were triggered by altered stomatal and mesophyll processes. Stomatal conductance changed in parallel with changes in mesophyll photosynthetic properties. In both the cultivars ACS activity and ethylene increased up to 3.0 mM ethephon, but 1.5 mM ethephon caused maximum effects on photosynthetic parameters. CONCLUSION: These results suggest that ethephon affects foliar gas exchange responses. The changes in photosynthesis in response to ethephon were due to stomatal and mesophyll effects. The changes in gS were a response maintaining stable intercellular CO2 concentration (Ci) under the given treatment in both the cultivars. Also, the high photosynthetic capacity cultivar, Varuna responded less to ethephon than the low photosynthetic capacity cultivar, RH30. The photosynthetic capacity of RH30 increased with the increase in ethylene evolution due to 1.5 mM ethephon application.
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