RESUMO
Complex living organisms possess qualities that cannot be reduced to the simple addition of quantities. Among such qualities are a specific form and a specific organization. Thinking about morphological aspects is a prime example of the qualitative approach to biological matters. Such a morphogenetic perspective has been continuously developed, both theoretically and experimentally, along the past century, even though it is now rather marginal within a mainstream dominated by molecular biology. However, the morphogenetic outlook can be applied to the understanding of complex biological phenomena, such as cancer. This phenomenon is currently explained as a cellular problem caused by specific gene mutations and/or specific loss of gene regulation. Nevertheless, cancer is a problem that affects the whole organism. Contemporary research based on the genetic paradigm of cancer causation has led to paradoxes and anomalies that cannot be explained within such a reductionist paradigm. Here it is proposed that real, non-experimental, sporadic cancer may be understood as a conflict between an organized morphology (the organism) and a part of such a morphology that drifts towards an amorphous state (the tumour). Thus, rare, sporadic cancer in children can be the result of early disruption of the developmental constraints before the organism has achieved its morphological maturity. While common sporadic cancer in aged individuals may ensue as a result of the weakening or exhaustion of the developmental constraints that determine the morphological stability of the organism, once the organism is past its reproductive prime.
Assuntos
Neoplasias/patologia , Criança , Cromossomos Humanos , Humanos , Morfogênese , Mutação , Neoplasias/genéticaRESUMO
The product of the p53 tumor suppressor gene has been implicated in safeguarding genomic stability by transactivating genes involved in cell cycle arrest, repair of DNA damage or induction of apoptosis. Several properties of p53 suggest that it might be directly involved in DNA repair processes. Eukaryotic DNA is highly organized in supercoiled loops anchored to the nuclear matrix. This organization is very important for cell function and survival, suggesting that repair of DNA damage must include both, the integrity of the double helix and the complex DNA topology. In this work, we studied the kinetics and efficiency of higher-order DNA structure repair in cells with normal and reduced levels of p53, and present evidence suggesting that p53 may be involved in the stabilization and/or repair of higher-order DNA structure.
Assuntos
Núcleo Celular/metabolismo , Reparo do DNA , Proteínas de Ligação a DNA , Proteína Supressora de Tumor p53/metabolismo , Centrifugação com Gradiente de Concentração , Dexametasona/farmacologia , Etídio , Feminino , Humanos , Proteínas Oncogênicas Virais/biossíntese , Papillomaviridae/genética , Fatores de Tempo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/deficiência , Raios Ultravioleta , Neoplasias do Colo do ÚteroRESUMO
In cells infected by herpesviruses, a sequence of nuclear changes during interphase, as well as chromosomal aberrations during mitosis, are commonly observed. These changes suggest the progressive modification of host-cell chromatin. Previous studies have shown that the early chromatin modifications in cells infected by herpes simplex virus type 1 (HSV1) are not due to extensive breakdown of host-cell DNA or disruption of the nucleosomal structure. We have previously shown that infection by HSV1 induces single-stranded breaks in the host-cell DNA early in the course of infection, and that such breaks lead to modifications in the higher-order structure of host-cell chromatin. Here we report that virus-induced DNA breaks produce permanent long-term effects on the state of supercoiling and organization of the nuclear DNA loops, comparable to the DNA loop disorganization produced by high (and irreparable) doses of ultraviolet radiation.