2. Carcinogenesis

Carcinogenesis is a slow process categorized by the acquirement over time of accumulated mutations and chromosomal changes caused by impairment in the genome that leads healthy cells to become deregulated [22]. During cancer development, are subjected monoclonal or polyclonal malignant cells [23] to a microevolutionary process [24] accumulating critical mutations in a crucial group of genes involved in cell division, apoptosis, DNA repair, and in other essential genes that control collective cell behavior. However, after some critical mutations in genes that maintain genetic stability in healthy cells, cancer cells turn into the mutator phenotype [25, 26], initiating a cascade of mutations through the genome that produces genetic heterogeneity in tumors [23]. This process provides cancer cells with selective advantages to colonize the patient's organism evading its natural defenses used to handle any cellular attack. Such benefits of neoplastic cells have been called the hallmarks of cancer and include six features: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis [27]. Transformed cells, then, instead of behaving altruistically and cooperatively, selfishly ignore any regulating signal and proliferate in an uncontrolled way forming tumors, invading organs and tissues, and spreading throughout the organism, colonizing it.

#### 2.1. ChemCar

ChemCar is a multistep process initiated by the electron attack to nucleophilic tissues or molecules, such as DNA, producing mutations that lead normal cells to become unregulated, proliferate, and then turn malignant [8, 9, 28]. Metabolic activation of procarcinogens produces highly reactive chemical species that yield to the overproduction of reactive oxygen and nitrogen species (ROS, NOS), which cause damage to DNA and other biomolecules [29, 30]. The current mutation theory of carcinogenesis considers it to be a complicated process that broadly consists of three phases or stages: initiation, promotion, and progression (for a review see [31–33]). Chemical carcinogens may act together or in sequence to initiate or promote carcinogenesis. The initiation stage is characterized by an irreversible dose-dependent genetic change that predisposes normal cells to evolve into a malicious and immortal state [27]. During initiation, cells are induced to proliferate, but not differentiate [33], inheriting mutations and thus producing initiated daughter cells. In the promotion stage, the initiated cells are clonally selected to expand through an increase in cell proliferation or by a decrease in cell death, the so-called apoptosis process [30]. Although promoter stimuli do not interact directly with the DNA, they can be damaged indirectly by OS, and gene expression can be altered by epigenetic mechanisms. Nevertheless, it is considered that promotion is a reversible stage because the elimination of the promoter produces regression in cell proliferation maybe by apoptosis [33]. Lesions in both initiation and promotion stages are yet to be considered as preneoplastic ones or benign neoplasias [32]. However, in the irreversible third state, they are transformed into malignant lesions, i.e., progression. Cell proliferation independent of stimulus characterizes this stage: faster growth, invasion, metastasis, and morphological, biochemical, and metabolic changes in transformed cells [33].
