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F Marks

Publications and source records attributed to F Marks.

At least 217 records · Page 12Linked to original sources

Ornithine decarboxylase activity, cell proliferation, and tumor promotion in mouse epidermis in vivo.

The effect of different phorbol esters and of mechanical treatment on the activity of ornithine decarboxylase in mouse epidermis in vivo was investigated. The strong promoter 12-O-tetradecanoylphorbol-13-acetate as well as the weak promoters phorbol dibenzoate and the 12-O-tetradecanoylphorbol-13-acetate analog 12-O-tetradeca-2-cis, 4-trans-6,8-tetraenoylphorobol-13-acetate strongly increased the activity of the enzyme and the intraepidermal level of putrescine, with a maximum at 5 hr after application, when applied in doses which evoke comparable proliferative and irritant responses in skin. The hyperplasiogenic but nonirritant and almost nonpromoting 4-O-methyl ether of 12-O-tetradecanoylphorbol-13-acetate did not show such effects. Mechanical removal of the uppermost horny layer led to a considerable increase of ornithine decarboxylase activity after 4 to 8 hr, while skin massage showed only a minute effect under conditions in which both treatments exhibit about the same mitogenic efficiency. Neither manipulation promotes tumor development. After skin massage, the induction of ornithine decarboxylase was influenced neither by treatments which alter the cyclic adenosine 3',5'-monophosphate level in epidermis (inhibition of phosphodiesterase, beta-adrenergic stimulation, and injection of dibutyryl cyclic adenosine 3',5'-monophosphate) nor by injection of epidermal G1 chalone. The results indicate that no clear-cut correlation exists between epithelial cell proliferation, development of hyperplasia, and tumor promotion on the one hand and an activation of epidermal ornithine decarboxylase on the other.

Animals↗

The effect of indomethacin on cell proliferation induced by chemical and mechanical means in mouse epidermis in vivo.

Pretreatment of mouse skin in vivo with indomethacin prevents the stimulation of epidermal cell proliferation caused by either removal of the horny layer or by application of phorbol ester TPA. The stimulatory effect of phorbol ester "TI8" is only partially inhibited, whereas the drug indomethacin has no effect on the proliferative response to skin massage or the hyperplasiogenic reaction induced by phorbol ester 4-0-methyl-TPA. These results show that depending on the stimulus, epidermal cell proliferation and hyperplasia can proceed either via an indomethacin sensitive or via an indomethacin insensitive pathway, and that indomethacin sensitivity is neither related to the hyperplasiogenic nor the tumor-promoting efficiency of the stimulus. Although TPA and 4-0-methyl-TPA are structurally closely related phorbol esters, they have different mechanisms of mitogenic action.

Animals↗

Induction of the formation of new hair follicles in mouse tail epidermis by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate.

The formation of new hair follicles was quantitatively demonstrated in the tail skin of adult mice in the course of a two-stage carcinogenesis experiment with 7,12-dimethylbenz(a)anthracene as an initiator and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate as a promoter, as well as in experiments with 12-O-tetradecanoylphorbol-13-acetate alone. Two kinds of follicular neogenesis could be distinguished. The most frequently encountered type was characterized by the organization of new follicles from the upper neck and orifice regions of already existing follicles. During their development, these new follicles remained in close apposition to the original follicles but, after having reached a critical size, split off to form fully independent follicles. In the second, type of follicular neogenesis, which occurred very rarely, the new follicles seemed to arise directly from the epidermis between two sets of hair triads; however, these follicles never reached their final stage and did not produce hairs. The formation of new hair follicles may be explained by a "dedifferentiation" of epidermal cells caused by the tumor promoter. Because of the paucity and advanced stage of the papillomas formed in tail skin after long-term treatment with 12-O-tetradecanoylphorbol-13-acetate, no reliable comment as to whether the papillomas derive from the hair follicles can be made.

9,10-Dimethyl-1,2-benzanthracene↗

Effect of mechanical stimulation on cell proliferation in mouse epidermis and on growth regulation by endogenous factors (chalones).

Mechanical stimulation of dorsal mouse skin by skin massage or removal of the horny layer results in a mutually comparable increase in DNA-labelling and mitotic activity. However, only after injury such as removal of the horny layer hyperplasia develops. This phenomenon, called "hyperplastic transformation" is characterized by a transient abolition of the epidermal G1 chalone responsiveness. There is some indication that the susceptibility to a heat labile factor, probably the epidermal G2 chalone, is not affected. Skin massage neither interferes with the responsiveness to epidermal G1 chalone nor induces "hyperplastic transformation". Mouse tail epidermis shows a "functional hyperplasia" and responds to the G1 chalone. To explain these observations, it is assumed that the epidermal stem cell population is heterogeneous consisting of G1 chalone-sensitive and G1 chalone-insensitive cells.

Animals↗