|Lecture Notes:: 25 March||
Get age effects at both extremes. As an example gastric acidity is lower in humans in both infants and the aged.
The mammalian fetus is a special situation - the mother is taking care of most of metabolism. The liver of the fetus is largely inactive in a variety of metabolic systems. This can result in both increased or decreased toxicity of compounds. For paracetamol, the toxicity is reduced since it must be activated by P450 which is low in neonate liver. Toxicity in this case is increasedon the other hand because glutathione is needed in detoxification, and it is also low, however, glutathione rises faster, so overall teh neonate is advantaged in this case. (Figure 5.30, p 163 in Timbrell 4th).
Liver disease is particularly noticeable, which is not surprising given its central role in toxin metabolism. Changes in plasma protein levels can impact thresholds etc., while malabsorption syndromes can influence the amount of toxin which enters the body.
Hormonal status can have significant impact on metabolism, and so can affect the actions of toxins. In particular the periodic variation in female sex hormones which cause growth and regression of tissues such as breast can lead to toxic impacts (e.g. breast cancer rates increase with number of lifetime periods). Other hormones such as thyroid and the pituitary hormones (i.e. growth hormone, ACTH, etc.) have general impacts on metabolism.
Toxic responses, how the organism is affected by toxins, are classified by toxic effect. There are four categories which are common in the literature:
Timbrell adds two additional categories, which are often treated as subcategories of tissue lesions:
We will begin our discussion with Chemical carcinogenesis. Cancer induction is a vast, complex, and controversial study.
First, what do we mean by cancer? Often think of cancers as rapidly dividing cell lines, but not always the case. Cancer involves a somatic cell line indulging in unrestrained, invasive proliferation. A cancer may be localized or metastasized (cells break free and establish new clones elsewhere in the body). Note that the process of carcinogenesis involves the cell line having a heritable trait for unrestrained growth, and an evolutionary process transforming a normal cell type to a cancer cell.
Mature cancer cell lines are often characterized by:
Cancer induction involves at least two kinds of events:
In general we can say
Last modified 25 March 2010
© RA Paselk 2001