Particles that reach the lower respiratory tract or pleura can induce a number of biological responses at the cellular and molecular levels, including inflammation, the generation of active oxygen species, lysis, and transformation [ Kane, 1993; Lehnert, 1993; Mossman, 1993]. The type and degree of response depends on a number of factors, including the particle's characteristics.
Inflammation is a process involving a complex cellular
response to adversity. This response takes many forms,
including the release of active oxygen species and cytokines
[ Kelley, 1990]. Active oxygen species (AOS) are molecules
that possess an unpaired electron (e.g., 
OH,
O
), so they are highly reactive and
damaging to cell membranes and deoxyribonucleic acid or DNA.
Cytokines are proteins produced by a cell in order to mediate
the activities of other cells or even to mediate its own
activities.
One of the principle cell types that regulate inflammation and lung defense is the macrophage [ Sibille and Reynolds, 1990], which, in addition to its role as a scavenger cell, is an important mediator of inflammation via the release of cytokines and AOS. The activation of macrophages results from exposure to certain minerals but not to all [ Kuhn and Demers, 1992], and it is a critical step in mineral-induced pathogenesis [ Driscoll, 1993; Mossman, 1993]. To achieve an integrated model for mineral-induced disease, one must determine the interrelationships between cellular and molecular responses (such as the activation of macrophages) and mineralogical properties.
Unfortunately, the mineralogical properties and geochemical
processes that activate macrophages or that affect other
cells in general are not known. Several possibilities have
been suggested, including particle morphology [ Hansen and
Mossman, 1987], surface charge [ Light and Wei, 1977], the
presence of acid sites on the surface [ Nash et al., 1966;
Nolan et al., 1981], the density of acid sites on the surface
[ Wiessner et al., 1988], electron-transfer at the mineral
surface [ Ghio et al., 1994], release of polyvalent cations to
the solution [ Lund and Aust, 1992], and the interactions
between mineral surfaces and constituents of cigarette smoke
[ Morimoto et al., 1993]. These mineralogical properties also
affect how a mineral interacts with a geological environment,
so it is not surprising that they are important in
physiological environments as well. Many of the geological
approaches used to study these mineralogical properties are
being applied successfully to problems involving
mineral-induced disease. For example, Hobza and Hurych [ Hobza and
Hurvch, 1978] used quantum-chemical calculations to assess
the potential effect of ion substitution in quartz on the
biological reactivity. They noted distinct changes in the
electronic structure of quartz following Al substitution or
incorporation of impurity elements, such as Li, Na, Mg, and
Fe. Elemental impurities are known to affect the biological
reactivity of quartz (see [ Langer, 1978] and references
therein). Gulumian et al. [ Gulumian et al., 1993] used
electron-spin resonance and M”ssbauer spectroscopy to study
the chemical changes resulting from a detoxification process
for crocidolite. The process involves treating the
crocidolite with ferric oxide salts. Guthrie et al. [ Guthrie
et al., 1992] used cation-exchanged zeolites to assess the
role of the exchangeable cation on zeolite cytotoxicity; they
found that the cation type has no significant effect on
cytotoxicity to epithelial cells. And Wiessner et al.
[ Wiessner et al., 1988] used various SiO
polymorphs to
assess the role of crystal structure on inflammation and
fibrosis; they found that crystal structure of the polymorph
plays an important role in determining biological response.
These few examples are not intended as a comprehensive review
of the literature; rather they illustrate the range of
geological approaches applied to this problem---from
quantum-chemical calculations to spectroscopic methods to
mineralogical strategies for experimental design.