Calcium glucarate prevents tumor formation in mouse skin.
OBJECTIVE
Calcium Glucarate (Cag), Ca salt of D-glucaric acid is a naturally occurring non-toxic compound present in fruits, vegetables and seeds of some plants, and suppress tumor growth in different models. Due to lack of knowledge about its mode of action its uses are limited in cancer chemotherapy thus the objective of the study was to study the mechanism of action of Cag on mouse skin tumorigenesis.


METHODS
We have estimated effect of Cag on DMBA induced mouse skin tumor development following complete carcinogenesis protocol. We measured, epidermal transglutaminase activity (TG), a marker of cell differentiation after DMBA and/or Cag treatment and [3H] thymidine incorporation into DNA as a marker for cell proliferation.


RESULTS
Topical application of Cag suppressed the DMBA induced mouse skin tumor development. Topical application of Cag significantly modifies the critical events of proliferation and differentiation TG activity was found to be reduced after DMBA treatment. Reduction of the TG activity was dependent on the dose of DMBA and duration of DMBA exposure. Topical application of Cag significantly alleviated DMBA induced inhibition of TG. DMBA also caused stimulation of DNA synthesis in epidermis, which was inhibited by Cag.


CONCLUSIONS
Cag inhibits DMBA induced mouse skin tumor development. Since stimulation of DNA synthesis reflects proliferation and induction of TG represents differentiation, the antitumorigenic effect of Cag is considered to be possibly due to stimulation of differentiation and suppression of proliferation.
Environmental Carcinogenesis Division, Industrial Toxicology Research Center, Post Box No. 80, Mahatma Gandhi Marg, Lucknow-226001, India.
Jaya
J
Singh
Krishna P
KP
Gupta
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000287:Administration, Topical; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000633:toxicity; D005260:Female; D005937:Glucaric Acid / Q000627:therapeutic use*; D051379:Mice; D012878:Skin Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D013936:Thymidine / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D011503:Transglutaminases; D005937:Glucaric Acid; D013936:Thymidine