Morphological transformation induced by chemical carcinogens is enhanced by the biologically active metabolite of vitamin D/sub 3/, 1. cap alpha. ,25-dihydroxycholecalciferol

Journal Article · Thu Mar 01 04:00:00 EST 1984 · Proc. Am. Assoc. Cancer Res.; (United States)

OSTI ID:6240154

Jones, C A; Callaham, M F; Huberman, E

The active metabolite of vitamin D/sub 3/, 1..cap alpha..,25-dihydroxycholecalciferol (1,25-(OH)/sub 2/D/sub 3/) was found to increase the frequency of morphologically transformed colonies induced by chemical carcinogens in the hamster embryo cell transformation assay. Treatment of the embryo cells with either benzo(a)pyrene, (+/-) 7..beta..,8..cap alpha..-dihydroxy-9..cap alpha..,10..cap alpha..-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene or N-methyl-N'-nitro-N-nitrosoguanidine for 3 days followed by treatment of the cells with 1,25-(OH)/sub 2/D/sub 3/ for 4 days resulted in an increase in the transformation frequency compared to cells treated with the carcinogen only. Reversing the order of the treatment (i.e., incubating the cells with 1,25-(OH)/sub 2/D/sub 3/ prior to benzo(a)pyrene treatment) did not result in such an enhancement. Vitamin D/sub 3/ and 24,25-dihydroxycholecalciferol, another metabolite of this vitamin, also enhanced the frequency of cell transformation but were less potent than 1,25-(OH)/sub 2/D/sub 3/. Pyrene, which is not carcinogenic, did not induce transformed colonies, nor did the combination of pyrene and 1,25-(OH)/sub 2/D/sub 3/ treatment result in the development of such colonies. Benzo(e)pyrene (B(e)P), which is considered as either an inactive or weak carcinogen, was also ineffective in inducing transformed colonies. However, in the two-stage protocol when B(e)P was used with 1,25-(OH)/sub 2/D/sub 3/, the authors observed a significant number of transformed colonies. These studies demonstrate that 1,25-(OH)/sub 2/D/sub 3/ resembles phorbol 12-myristate 12-acetate in its capacity to enhance morphological transformation in carcinogen-treated hamster embryo cells. These results suggest that this vitamin D/sub 3/ metabolite may act as a natural promoter of carcinogenesis in fibroblastic cells.

• Research Organization: Argonne National Lab., IL
• OSTI ID: 6240154
• Journal Information: Proc. Am. Assoc. Cancer Res.; (United States), Journal Name: Proc. Am. Assoc. Cancer Res.; (United States) Vol. 25; ISSN PAACA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
BENZOPYRENE
CARCINOGENESIS
CARCINOGENS
CELL TRANSFORMATIONS
CONDENSED AROMATICS
EMBRYONIC CELLS
HAMSTERS
HYDROCARBONS
MAMMALS
METABOLITES
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
RESPONSE MODIFYING FACTORS
RODENTS
SYNERGISM
VERTEBRATES
VITAMIN D
VITAMINS