1. The importance of CYP3A enzymes in drug metabolism and toxicology has yielded a wealth of information on the structure, function and regulation of this subfamily and recent research emphasis has been placed on the human forms, namely CYP3A4, CYP3A5, CYP3A7 and CYP3A43. 2. The current review will focus on the receptor-dependency of CYP3A regulation and includes consideration of the regulatory roles of the glucocorticoid (GR), pregnane X (PXR) and constitutive androstane (CAR) receptors. 3. Emphasis has been placed on the topics of expression and substrate specificity, assessment of induction, species differences in induction, CYP3A promoter sequences and regulation of gene expression, structural and functional aspects of receptor-mediated, CYP3A gene activation, receptor variants and interindividual variation in human CYP3A expression, the latter encompassing environmental, physiological and genetic aspects. 4. An outline of future research needs will be discussed in the context of receptor-mediated molecular mechanisms of CYP3A gene regulation and the impact on interindividual variations in CYP3A expression. 5. Taken collectively, this review highlights the importance of understanding the molecular mechanisms of CYP3A induction as a means of rationalizing human responses to many clinically used drugs, in addition to providing a mechanistically coherent platform to understand and predict interindividual variations in response and drug-drug interactions.

The mating system of the ascomycete forest pathogen Crumenulopsis sororia was investigated using naturally occurring isozyme genetic markers and appropriate genetic models. Mating was found to occur exclusively through outcrossing. For 8 of the 25 apothecia scored, more than one mate parent was involved in giving rise to ascogenous hyphae. Substantial subdivision occurs within the population which is composed of genetically differentiated subpopulations occupying discrete lesions on host trees.

Twenty families of single‐ascospore isolates of the canker pathogen Crumenulopsis sororia were collected from eight trees of Pinus sylvestris in a native pinewood. Measurements were made of growth rate of each isolate in the presence and absence of a saturating atmosphere of the five principal monoterpenes of P. sylvestris cortical oleoresin (α‐pinene, β‐pinene, 3‐carene, β‐myrcene and limonene). All monoterpenes significantly reduced the mean linear growth rate of the C. sororia population. However, there was highly significant genetic variation among isolates in their tolerance of all five monoterpenes. The extent of genetic variation was greatest for β‐myrcene and limonene tolerance, and least for α‐pinene and 3‐carene tolerance. Significant positive correlations between tolerance of different monoterpenes were found, implying the presence of tolerance mechanisms common to a range of compounds.

Abstract. -In response to infection by shoot infecting pathogens, Scots pine releases cortical resin into affected tissues. The resin contains a mixture ofmonoterpene compounds (a-pinene, tl-pinene, 3-carene, tl-myrcene, limonene and tl-phellandrene) that retard the growth ofa range of pathogens. The proportion of each monoterpene in the resin shows substantial variation among trees within a population. Thus pathogens on different trees encounter quite different monoterpene environments. To investigate the evolutionary response of pathogens to the chemically heterogeneous environment provided by Scots pine, isolates of the ascomycete canker pathogen Crumenulopsis sororia were collected from trees within a range of natural Scots pine populations. Growth rates ofthese isolates were measured in the presence and absence offive host monoterpenes. Substantial heritable variation for growth rate in the presence and absence of monoterpenes, and for monoterpene tolerance was recorded, suggesting the potential for the evolution ofchemically specialized pathogen subpopulations on different trees within a wood. However, genetic correlations between growth rates in different monoterpene environments and between tolerance of different monoterpenes were either positive or non-significant, and there was no evidence of "tradeoffs" in performance under different monoterpene regimes. The results suggest that, on its own, the presence of monoterpene variability within Scots pine will not lead to disruptive selection on the C. sororia population. The relationship between defensive chemical diversity and pest resistance is discussed in the light of these results.

No abstract