Comparison of two-stage epidermal carcinogenesis initiated by 7,12-dimethylbenz(a)anthracene or N-methyl-N'-nitro-N-nitrosoguanidine in newborn and adult SENCAR and BALB/c mice.

In order to define factors which determine susceptibility to chemical carcinogenesis, mice sensitive (SENCAR) and resistant (BALB/c) to epidermal carcinogenesis were studied under several treatment conditions for sensitivity to initiation by 7,12-dimethylbenz(a)anthracene or N-methyl-N'-nitro-N-nitrosoguanidine and promotion by 12-O-tetradecanoylphorbol-13-acetate. In newborns of both strains, topical application of initiator was much less effective than in adults. However, initiation by i.

Phorbol ester-induced anchorage independence and its antagonism by retinoic acid correlates with altered expression of specific glycoproteins.

Since tumor promoting phorbol esters produce a variety of glycoprotein synthesis changes and since retinoids act both as antipromoters and modulators of glycoprotein synthesis, we sought to ascertain whether specific changes in glycoprotein synthesis might be targets both for the promoting action of phorbol esters and for the antipromoting actin of retinoids. In this report we present evidence that tumor promoting but not nonpromoting phorbol esters produce decreased levels of 180,000 and 150,000 mol, wt, glycoproteins in mouse JB-6 cells which are promotable to tumor cell phenotype by phorbol esters. These relatively specific decreases are blocked by an antipromoting concentration of retinoic acid, thus suggesting that decreases in 180K and 150K glycoproteins may play a role in promotion of transformation.

Tumor promoter produces anchorage independence in mouse epidermal cells by an induction mechanism.

The irreversible shift in anchorage independence by phorbol ester responsive mouse epidermal cell lines appears to occur not by a mechanism involving selection of preexisting transformants but by induction of a new phenotype.

A cell culture assay for tumor-promoter-dependent progression toward neoplastic phenotype: detection of tumor promoters and promotion inhibitors.

Mouse epidermal cell lines have been identified which respond to tumor-promoting (but not nonpromoting) phorbol esters with an irreversible shift in anchorage independence, an in vitro marker of neoplastic phenotype. This response may be analogous to a later stage of tumor promotion in vivo. The shift occurs at TPA concentrations as low as 0.

Decrease of epidermal histidase activity by tumor-promoting phorbol esters.

The potent skin tumor promoter (12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulates epidermal macromolecular synthesis as well as proliferation, but little is known of specific functional aberrations produced by TPA. This report presents results of a study on the effects of TPA on epidermal histidase (L-histidine ammonia lyase), an enzyme found in normal epidermis but not in dermis or in mouse squamous cell carcinomas. Histidase activity was assayed on postmitochondrial supernatants obtained from hairless mouse epidermis after removal by keratotome.