Mitotic activity

In addition to effects on biochemical reactions, the inhibitors may influence the permeability of the various cellular membranes and through physical and chemical effects may alter the structure of other subcellular structures such as proteins, nucleic acid, and spindle fibers. Unfortunately, few definite examples can be listed. The action of colchicine and podophyllin in interfering with cell division is well known. The effect of various lactones (coumarin, parasorbic acid, and protoanemonin) on mitotic activity was discussed above. Disturbances to cytoplasmic and vacuolar structure, and the morphology of mitochondria imposed by protoanemonin, were also mentioned. Interference with protein configuration and loss of biological activity was attributed to incorporation of azetidine-2-carboxylic acid into mung bean protein in place of proline. 

Smooth muscles do more than contract and the regulation of the mitotic activity of vascular smooth muscle is important in the maintenance of the oxygen supply to tissues and the genesis of hypertension of non-renal origin. Secretion activities of smooth muscle are just beginning to be appreciated. 

Gould, K. L Moreno, S., Tonks, N. K., and Nurse, P. (1990). Complementation of the mitotic activator, p80c r25, by a human protein-tyrosine phosphatase. Science 250 1573-1576. 

Suppression of mitotic activity Trichlorfon, carbaiyl, thiram, nitro-aldicarb... 

SC Miller, MD Donovan. (1982). Effect of poloxamer 407 gel on the mitotic activity of pilocarpine nitrate in rabbits. Int J Pharm 12 147-152. 

Eleven male volunteers aged 20-30 years ingested lead acetate for 49 days. PbB levels were kept at approximately 40 pg/dL. The frequency of chromosome aberrations was assayed after lymphocyte culture for 72 hours and found to be no different from that of 10 controls. The lymphocytes from lead-exposed subjects did show a higher mitotic activity (Bulsma and DeFrance 1976). 

As expected, a lower number of RAT, that is, a mitodepressive effect, is observed in plant species treated with MH alone (data not shown) (Ferrara et al. 2001). With respect to the treatment with MH, any combination HS + MH appeared not to modify the mitotic activity (RAT number) of cells in V. faba, whereas it caused a slight reduction of the RAT number in P. sativum, and yielded contrasting results in A. cepa (data not shown) (Ferrara et al. 2001). 

Kawaguchi K, Fujii S, Konishi I, Nanbu Y, Nonogaki H, Mori T (1989) Mitotic activity in uterine leiomyomas during the menstrual cycle. Am J Obstet Gynecol 160 637-641... 

Tiltman AJ (1985) The effect of progestins on the mitotic activity of uterine fibromy-omas. Int J Gynecol Pathol 4 89-96... 

Peripheral blood cultures are stimulated to divide by the addition of a T cell mitogen such as phytohaemagglutinin (PHA) to the culture medium. Mitotic activity is at a maximum at about 3 days but begins at about 40 h after PHA stimulation and the chromosome constitution remains diploid during short-term culture (Evans and O Riordan, 1975). Treatments should commence at about 44 h after culture initiation. This is when cells are actively proliferating and cells are in all stages of the cell cycle. They should be sampled about 20 h later. In a repeat study the second sample time should be about 92 h after culture initiation. Morimoto et al. (1983) report that the cycle time for lymphocytes averages about 12-14 h except for the first cycle. 

Cell proliferation, predominantly in the proximal tubules, occurred in Wistar rats following a single oral dose of 100 mg/kg 1,2-dibromoethane in corn oil. Mitotic activity peaked at 30 hours. Lack of any histologic evidence of tubular necrosis between 8-48 hours after treatment indicates that such proliferation was not a regenerative response (Ledda-Columbano et al. 1987b). 

Fetner has also demonstrated chromatid breaks in a human tissue-culture cell line exposed to ozone at 8 ppm for 5 min. Other tissue-culture studies include that of Sachsenmaier et who noted tetraploidy and other chromosomal abnormalities in embryonic chick fibroblasts exposed to ozone and a decrease in transplantability of mouse ascites tumor cells. In addition, Pace et demonstrated an interference by ozone with mitotic activity in two tissue-culture cell lines. More recently, Booher et al. reported that lung cells exposed in culture to ozone concentrations as low as 0.3 ppm demonstrated an inhibition in growth that was proportional to the ozone concentration. 

Loss of hair results from injury to hair follicles gastrointestinal disturbances, such as diarrhea, from inadequate replacement of enterocytes whose life span is limited to a few days nausea and vomiting from stimulation of area postrema chemoreceptors (p. 330) and lowered resistance to infection from weakening of the immune system (p. 300). In addition, cytostatics cause bone marrow depression. Resupply of blood cells depends on the mitotic activity of bone marrow stem and daughter cells. When myeloid proliferation is arrested, the short-lived granulocytes are the first to be affected (neutropenia), then blood platelets (thrombopenia) and, finally, Liillmann, Color Atlas of Pharmacology... 

Nonylphenol has recently been shown to have estrogenic properties, triggering mitotic activity in rat endometrium and cell proliferation in estrogen-sensitive tumor cells. Potential toxicity to humans who may be exposed to nonylphenol through leaching of plastics has not been determined. 

Myocyte replication is the failing heart s attempt to compensate for a limited capacity for hypertrophy. When Urbanek et al. [37] used Ki-67 (a nuclear protein expressed during cell division) to assess the mitotic activity of myocytes, they observed significantly greater mitotic activity at infarct border zones than in distant myocardium or undiseased control hearts. The evidence that cardiac myocytes divide shortly after a myocardial infarction led investigators to search for the origin of the dividing myocytes [82]. This culminated in the description of resident CSCs [35-37]. 

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