A plausible model for reversal of neoplastic transformations in plants based on multiple steady states.

Abstract

We offer a plausible interpretation of some experiments on the reversal of neoplastic transformations in plants. We suggest that normal cells and tumorous cells represent multiple stable-steady states corresponding to a reaction feedback mechanism. The (autocatalytic) feedback loop is constructed from observations on the role played by myo-inositol: it increases the permeability of ions through the membrane and the biosynthetic pathway to myo-inositol is activated by ions. Provided that the permeabilities of nutrients (sugars and salts) are a product-enhanced function of myoinositol, then we have a (oversimplified) model that can exhibit multiple stationary stable states, one or two depending on the exogenous nutrients and myo-inositol concentrations, and reversible and irreversible transitions from one of these states to the other are possible. From this model, straightforward simple experiments are suggested. We also propose that recent models dealing with the intracellular calcium regulation by hormones, where one key step requires the hydrolysis of inositol phospholipids, take into account free myo-inositol and endogeneous hormone concentrations (e.g., auxins).Hairy root disease and crown gall tumors are neoplastic growth on plants incited by virulent strains ofthe soil bacteria Agrobacterium rhyzogenes and Agrobacterium tumefaciens, respectively. These processes are associated with the incorporation in the plant host cells of large plasmids (Ri and Ti plasmids, respectively) harbored by these bacteria. In both cases these plasmids contain two regions necessary for tumorigenesis. They include the transferred DNA (T-DNA) region and the vir (virulence) region. The T-DNA contain genes that (i) specify the oncogenic phenotype (through hormone biosyntheses) and (ii) direct the production and secretion of low molecular weight, tumor-specific compounds called opines (e.g., octopine and nopaline). As a result, the transformed plant cells can grow in sterile cultures without addition ofthe phytohormones auxins and cytokinins (1, 2).Most examples of reversal of the crown gall tumorous states studied (3-9), rarely capable of rooting and sensitive to surinfection by Agrobacterium, have turned out to be explained by either deletion (10-13) or methylation of part or the totality of T-DNA sequences (14,15). Hairy root tumors induced by Agrobacterium strains carrying mannopine Ri plasmids can, however, spontaneously regenerate plants, albeit with altered morphology, that still contain and express T-DNA genes (16)(17)(18)(19).Striking formal similarities exist between crown gall transformation and habituation. The term habituation refers to the loss of a requirement for externally supplied phytohormones by plant tissues and cells in culture (20). Habituation is a form of neoplastic transformation involving heritable, progressive changes in cell phenotype that can result in autonomous growth. However, habituation occurs in the absence of a recognizable infectious agent and appears to have an epigenetic basis; it is re...

Special symposium: In vitro plant recalcitrance loss of plant organogenic totipotency in the course of In vitro neoplastic progression

“…the formation of organized structures such as roots or shoots, either spontaneously or after treatment with plant growth regulators. The regeneration of complete plants from a great number of habituated clones, as well as from fully transformed single-cell clones isolated from a young crown gall strain, has been presented as proof that both processes, habituation and Agrobacterium-transformation, are reversible Melchers, 1969, 1977;Hervagault et al, 1991;Syono and Fujita, 1994). The chimeric nature of a tumor, i.e.…”

Multistabilité, oscillations et chaos dans les systèmes biologiques.

“…Qui doute pour autant que par son degré d'abstrac-tion, une carte ou un plan est mieux à même de nous orienter que la multitude de signes contradictoires non pertinents que recèle la réalité concrète de l'environnement local ? Les modèles dynamiques dépassant le simple cadre des schémas à deux variables décrits plus haut sont aujourd'hui appliqués à l'interprétation d'un grand nombre de processus cellulaires, physiologiques et complexes, liés au developpement (cycle cellulaire [42], différenciation [43], morphogenèse [44]). Leur intérêt conceptuel reste en grande partie masqué aux expérimentateurs par l'exigence de réfutabilité que ceux-ci croient devoir leur appliquer.…”

Bistability without Hysteresis: Electrochemically Driven Coupled Substrate Cycles

“…In such cases, the system can jump from one branch of (stable) steady states to the other but cannot undergo the reverse transition when the control parameter is varied across the bistability domain. The transition is therefore said to be irreversible. − Moreover, the analysis of the conditions under which bistability occurs in the absence of hysteresis in simple theoretical models for chemical systems based on fully reversible kinetic has demonstrated that the phenomenon is not an artifact produced by approximations in the derivation of the evolution equations …”

“…The transition is therefore said to be irreversible. [15][16][17][18][19][20][21][22][23][24][25] Moreover, the analysis of the conditions under which bistability occurs in the absence of hysteresis in simple theoretical models for chemical systems based on fully reversible kinetic has demonstrated that the phenomenon is not an artifact produced by approximations in the derivation of the evolution equations. 26 In the present communication we consider the dynamic and steady-state behaviors of a multienzyme system arranged in three coupled substrate cycles and operating under thermodynamically open conditions by in-and outfluxes of substrate and products (CSTR).…”