diethyl-maleate and Skin-Neoplasms

Single topical application of jute batching oil (JBO-P) elevated the status of enzyme GSSG-reductase in mouse skin and multiple applications produced a persistent increase in the enzyme levels. Also an increase in NADPH-dependent GSSG-reductase activity was registered after single topical application of known carcinogenic polyaromatic hydrocarbons (PAHs), e.g. benzo(a)pyrene (BaP), 7,12-dimethyl-benzanthracene (DMBA) and 3-methylcholanthrene (3-MC). This suggests that the change in GSSG-reductase activity induced by JBO-P is intrinsic to its tumorigenic activity rather than the toxic effect of the oil. Pretreatment of mouse skin with diethylmaleate (DEM), an SH-inactivating agent, increases the latent period of JBO-P induced tumorigenesis. No tumour was recorded in animals belonging to Group IV (DEM + JBO) while in animals belonging to Group II (JBO-P alone) 100% tumorigenesis was recorded during the period of study (i.e. up to 20 wk).

Topics: Animals; Carcinogens; Female; Glutathione Reductase; Maleates; Mice; Mineral Oil; Skin Neoplasms

The role of glutathione (GSH) in skin tumor promotion was ascertained in the present study by investigating the effect of the GSH depletor, diethyl-maleate (DEM), on the tumor-promoting ability of TPA in DMBA-initiated mouse skin. DEM lowered the tumor yield and the tumor incidence by 80% (p less than 0.001) in the DMBA + TPA treated group. The rate of tumor formation was also found to be influenced by DEM. The results suggest that clonal expansion of tumor-initiated cells, stimulated by TPA, depends upon the availability of reduced GSH in the tissue. The mechanism by which depletion of reduced GSH could result in inhibition of skin tumor promotion is not known. However, inactivation of GSH and thus blockage of the physiological function of reduced GSH in the biochemical events obligatory to tumor-cell proliferation in mouse skin could be the possible mechanisms providing effective control over proliferation of tumor cells.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Female; Glutathione; Maleates; Mice; Skin Neoplasms; Tetradecanoylphorbol Acetate

The tumour-promoting activity of methyl ethyl ketone peroxide (MEKP) was tested on the skin of hairless mice using a two-stage initiation-promotion protocol. When ultraviolet radiation in the UVB region (280-320 nm) was used as tumour initiator, MEKP showed weak promoting activity. The promotional activity of MEKP was potentiated by diethyl maleate, which is known to deplete intracellular glutathione, suggesting that lipid peroxidation may be important in the tumour promotion.

Topics: Acetone; Administration, Topical; Animals; Butanones; Carcinogens; Dibutyl Phthalate; Drug Synergism; Female; Lipid Peroxides; Male; Maleates; Mice; Mice, Hairless; Peroxides; Skin Neoplasms; Ultraviolet Rays