Dose-response relationships and the effect of age and latency period on the expression profile of laminin in irradiated rat mandibular glands.
OBJECTIVE
The extent of radiogenic salivary tissue damage (direct cell damage, reactive cell infiltration, increasing fibrosis) depends on the radiation dose (RD), the fractionation (FN) and the localisation of the salivary gland (SG) in the radiation field (RF). Because the histological damage is characterized by cellular and structural alterations and because extracellular matrix proteins, for example laminin (LA), are among the main components of the basement membrane (BM), which is considered to possess cell- and tissue structure-regulating functions, we set out to describe radiogenic BM changes.


METHODS
In 124 rat mandibular SG we investigated HE-stained sections and the LA staining profile (LASP) dependent on age [1 year (y) vs. 1 1/2 y], on FN [2 Gy/day up to a total dosage of 20/40/60 Gy (X-rays)], on RF [(left head and neck area); inside (left-sided SG) vs. outside (right-sided SG) RF] and on the latency of irradiation (1/2 y vs. 1 y) using immunohistochemical methods and multivariate analysis.


RESULTS
The immunoreactivity of the polyclonal antibody in the rat did not differ from the LASP in humans. LA was detected at variable levels in the glandular tissue, in vascular walls (without staining in the adventitia) and in nerve tissue (NT). No reaction was found in the capsule and the trabecula. In irradiated SG most tissue structures, including the vascular wall and NT, showed significantly stronger staining (both increased intensity and more extended expression). With increasing RD from 20 Gy to 60 Gy we found an increasing staining reaction. In addition, conglomerated LA depots were noted, especially in ares of disturbed or former acini of glands exposed to 60 Gy. The LASP up to 20 Gy was non-uniform and did not differ significantly from that in controls. A remarkable finding was the similar dose-dependent increase in staining reaction on both sides in several tissues of irradiated animals. Predominantly, however, we found considerably greater increases in staining in directly exposed glands than in out-of-field glands. Age and time since irradiation had no significant effect on staining.


CONCLUSIONS
The BM constituent LA showed dose-dependent increases in expression--analogous to positively dose-dependent increasing SG tissue damage--which could contribute to disturbed cell-matrix interaction and SG radiation damage. Several parenchymal structures may be more sensitive to possible scattered radiation.
Bartel-Friedrich
S
S
Department of Otorhinolaryngology, University Hospital, Martin Luther University Halle-Wittenberg, Magdeburger Str. 12, 06097 Halle a.d.S., Germany.
Friedrich
R E
RE
Lautenschläger
C
C
Holzhausen
H J
HJ
D000367:Age Factors; D000818:Animals; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D020869:Gene Expression Profiling; D007797:Laminin / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*
D007797:Laminin